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1. Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study

Author: Stéphanie Guillet, Valentine Loustau, Emmanuelle Boutin, Anissa Zarour, Thibault Comont, Odile Souchaud-Debouverie, Nathalie Costedoat Chalumeau, Brigitte Pan-Petesch, Delphine Gobert, Stéphane Cheze, Jean Francois Viallard, Anne-Sophie Morin, Gaetan Sauvetre, Manuel Cliquennois, Bruno Royer, Agathe Masseau, Louis Terriou, Claire Fieschi, Olivier Lambotte, Stéphane Girault, Bertrand Lioger, Sylvain Audia, Karim Sacre, Jean Christophe Lega, Vincent Langlois, Alexandra Benachi, Corentin Orvain, Alain Devidas, Sebastien Humbert, Nicolas Gambier, Marc Ruivard, Virginie Zarrouk, Mikael Ebbo, Lise Willems, Lauriane Segaux, Matthieu Mahevas, Bassam Haddad, Marc Michel, Florence Canoui-Poitrine, Bertrand Godeau, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de référence maladie rare des cytopénies auto-immunes de l'adulte (GECAI - Hôpital Henri-Mondor - UPEC), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Service de Génomique Fonctionnelle, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie biologique [CHU Limoges], and CHU Limoges
Subjects: Purpura, Thrombocytopenic, Idiopathic, Immunology, Pregnancy Complications, Hematologic, Infant, Newborn, Cell Biology, Hematology, Biochemistry, Cohort Studies, Thrombocytopenia, Neonatal Alloimmune, Pregnancy, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Prospective Studies, Retrospective Studies
Abstract: The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (
Published: 2022

2. Les échanges plasmatiques ne semblent pas être associés à un meilleur pronostic chez les patients avec une atteinte pulmonaire rapidement progressive d’une dermatomyosite anti-MDA5

Author: P. Bay, M. Pineton De Chambrun, V. Rothstein, M. Mahevas, A. Roux, B. Zuber, D. Israël-Biet, B. Hervier, A. Tazi, L. Mouthon, A. Mekinian, C. Deligny, R. Borie, A. Meyer, P. Priou, L. Savale, P.Y. Brillet, H. Nunes, Y. Allenbach, Y. Uzunhan, Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Marie-Lannelongue, Université Paris Nord (Paris 13), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service de Pneumologie [AP-HP Hôpital Avicenne, Bobigny]
Subjects: [SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine
Abstract: International audience
Published: 2022

3. Insights into<scp>anti‐D</scp>formation in carriers of<scp>RhD</scp>variants through studies of<scp>3D</scp>intraprotein interactions

Author: Aline Floch, France Pirenne, Aurélie Barrault, Btissam Chami, Cécile Toly‐Ndour, Christophe Tournamille, Alexandre G. Brevern, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Etablissement Français du Sang [Créteil], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de Médecine Fœtale [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université de La Réunion (UR), Université des Antilles (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), and TOURNAMILLE, Christophe
Subjects: Tropocollagen, Heterozygote, RHD, Rho(D) Immune Globulin, homology modeling, Immunology, 030204 cardiovascular system & hematology, Epitope, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Antigen, Pregnancy, intraprotein interactions, Extracellular, Humans, Immunology and Allergy, Homology modeling, Alleles, Retrospective Studies, Genetics, chemistry.chemical_classification, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Membrane Glycoproteins, biology, Point mutation, Blood Proteins, Hematology, antibody formation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Transmembrane protein, 3. Good health, Amino acid, Amino Acid Substitution, chemistry, Structural Homology, Protein, RHCG, Mutation, biology.protein, Female, 030215 immunology
Abstract: International audience; Background: Many RhD variants associated with anti-D formation (partial D) in carriers exposed to the conventional D antigen carry mutations affecting extracellular loop residues. Surprisingly, some carry mutations affecting transmembrane or intracellular domains, positions not thought likely to have a major impact on D epitopes.Study design and methods: A wild-type Rh trimer (RhD1 RhAG2 ) was modeled by comparative modeling with the human RhCG structure. Taking trimer conformation, residue accessibility, and position relative to the lipid bilayer into account, we redefine the domains of the RhD protein. We generated models for RhD variants carrying one or two amino acid substitutions associated with anti-D formation in published articles (25 variants) or abstracts (12 variants) and for RHD*weak D type 38. We determined the extracellular substitutions and compared the interactions of the variants with those of the standard RhD.Results: The findings of the three-dimensional (3D) analysis were correlated with anti-D formation for 76% of RhD variants: 15 substitutions associated with anti-D formation concerned extracellular residues, and structural differences in intraprotein interactions relative to standard RhD were observed in the others. We discuss the mechanisms by which D epitopes may be modified in variants in which the extracellular residues are identical to those of standard RhD and provide arguments for the benignity of p.T379M (RHD*DAU0) and p.G278D (RHD*weak D type 38) in transfusion medicine.Conclusion: The study of RhD intraprotein interactions and the precise redefinition of residue accessibility provide insight into the mechanisms through which RhD point mutations may lead to anti-D formation in carriers.
Published: 2021

4. ADAMTS13 and von Willebrand factor assessment in steady state and acute vaso‐occlusive crisis of sickle cell disease

Author: Julien Demagny, Anoosha Habibi, Sandrine Benghezal, Aurélie Driss, Françoise Driss, Alain Stepanian, Louis Affo, Nadia Anguel, Agnès Veyradier, Paul Coppo, Sophie Capdenat, Damien Roux, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Louis Mourier - AP-HP [Colombes], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, von Willebrand factor, 030204 cardiovascular system & hematology, Asymptomatic, Gastroenterology, 03 medical and health sciences, vaso‐occlusion, 0302 clinical medicine, Von Willebrand factor, Interquartile range, hemic and lymphatic diseases, Internal medicine, medicine, thrombosis, biology, lcsh:RC633-647.5, business.industry, Brief Report, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, Original Articles ‐ Thrombosis, medicine.disease, ADAMTS13, Thrombosis, Acute chest syndrome, 3. Good health, Cohort, biology.protein, sickle cell disease, medicine.symptom, business, Vaso-occlusive crisis, 030215 immunology
Abstract: International audience; Background: Sickle cell disease (SCD) is characterized by vaso‐occlusive crisis (VOC), acute chest syndrome (ACS) and multiorgan failure (MOF) complicated by thrombosis. Von Willebrand factor (VWF) is a strong marker of SCD‐related endothelial injury.Objectives: To decipher the role of VWF and its specific‐cleaving metalloprotease, ADAMTS13, in the vaso‐occlusive and thrombotic process of SCD.Patients/Methods: We investigated the VWF antigen (Ag), ADAMTS13 activity, ADAMTS13 Ag and ADAMTS13 IgGs in a cohort of 65 patients with SCD prospectively enrolled in a 20‐month period from three centers. Patients were divided into two groups: an asymptomatic group (n = 30) with treated or untreated SCD at steady state, and a VOC/ACS group (n = 35) with SCD with VOC/ACS requiring either medical management or intensive care management for MOF.Results and Conclusions: VWF:Ag levels were increased (median, 167 IU/dL; interquartile range [IQR], 124 ‐ 279), especially in patients with VOC SCD (227 IU/dL; IQR, 134‐305; P = .04), and positively correlated with inflammatory markers (P < .02). Median ADAMTS13 activity was normal (70 IU/dL; IQR, 60‐80), but 7 patients exhibited a partial deficiency between 25 and 45 IU/dL. ADAMTS13 activity/VWF:Ag ratio, however, did not change during VOC. Median ADAMTS13:Ag was slightly decreased (611 ng/mL; IQR, 504‐703) with no significant difference between groups. Surprisingly, ADAMTS13 IgGs were detected in 33 (51%) of our patients. We conclude that, in SCD, VWF:Ag and nonrelevant ADAMTS13 IgGs may reflect the severity of the inflammatory vasculopathy enhancing vaso‐occlusive and thrombotic complications.
Published: 2021

5. Impact of Carotid Geometry on Sickle Cell Diseases-Related Cerebral Vasculopthy Development

Author: Nguyen-Peyre, Kim-Anh, Liu, Weiqiang, Papamanolis, Lazaros, Kassasseya, Christian, Belkeziz, Nour, Amar, Valentin, Nahas, Gabriel, Eckert, Saskia, Vedel, Pierre, Lenoir, Laurène, Drémont, Katy, Cleophax, Sabine, Pirenne, France, Segonds, Frédéric, Verlhac, Suzanne, Vignon-Clementel, Irene, Bartolucci, Pablo, IMRB - 'NeuroPsychologie Interventionnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), SImulations en Médecine, BIOtechnologie et ToXicologie de systèmes multicellulaires (SIMBIOTX ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire Conception de Produits et Innovation (LCPI), Génétique et Physiopathologie des Maladies Cérébro-Vasculaires (U1161 / UMR_S 1161), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Île-de-France Mondor], CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Immunology, Cell Biology, Hematology, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2022

6. In silico and Functional Studies for Classification of EPAS1/HIF2A Genetic Variants Identified in Patients with Erythrocytosis

Author: Karaghiannis, Valéna, Maric, Darko, Garrec, Céline, Maaziz, Nada, Buffet, Alexandre, Antunes, Vincent, Le Roy, Amandine, Airaud, Fabrice, Aral, Bernard, Schmitt, Loic, Corbineau, Sébastien, Mansour-Hendili, Lamisse, Lesieur, Valentine, Rimbert, Antoine, Laporte, Fabien, Delamare, Marine, Bezieau, Stephane, Cassinat, Bruno, Galactéros, Frédéric, Gimenez-Roqueplo, Anne-Paule, Burnichon, Nelly, Cario, Holger, Wijk, Richard Van, Bento, Celeste, Blouet, Anaise, Bouteloup, Juliette, Boyer Perrard, Françoise, Bruce, Aisha Aiko, Cayssials, Emilie, Casadevall, Nicole, Cherel, Brieuc, Couec, Marielaure, Drevon, Louis, Dumesnil, Cecile, Lamy de la Chapelle, Thierry, Gambart, Marion, Garcon, Loic, Granel, Brigitte, Hirsch, Pierre, Lahary, Agnès, Mejri, Amira, Meunier, Sandrine, Nicolini, Franck, Raffoux, Emmanuel, Ranta, Dana, Schleinitz, Nicolas, Valentin, Jean Baptiste, Wemeau, Mathieu, Girodon, Francois, Hoogewijs, David, Gardie, Betty, Hermine, Olivier, Université de Fribourg = University of Fribourg (UNIFR), Centre hospitalier universitaire de Nantes (CHU Nantes), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Cardiology Department, Thorax Clinic Institute, Hospital Cliınic, Institut d'Investigacions Biomèdiques [Barcelona], Universitat de Barcelona (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Sorbonne Paris Cité (USPC), Réparation et Transcription dans les cellules Souches (Equipe - U967 INSERM), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Références Cancers Rares (PREDIR), INCA, Institut national du cancer [Boulogne] (INCA), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2022

7. Detection and follow-up of a soluble alpha-haemoglobin pool in the red cells of stored blood units

Author: Domingues-Hamdi, Elisa, Vasseur, Corinne, Bodivit, Gwellaouen, Jouard, Alicia, De Ménorval, Marie-Amélie, Pirenne, France, Chadebech, Philippe, Baudin-Creuza, Véronique, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité, Etablissement Français du Sang [Île-de-France Mondor], BAUDIN-CREUZA, Véronique, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Erythrocytes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Hemoglobins, Blood Preservation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Blood Components and Regenerative Medicine, Follow-Up Studies
Abstract: International audience; No abstract available
Published: 2022

8. Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

Author: Frédéric Galactéros, Sadaf Pakdaman, Elisa Domingues-Hamdi, Corinne Vasseur, Véronique Baudin-Creuza, Vasseur, Corinne, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), EFS, and Hôpital Henri Mondor
Subjects: Adult, Erythrocyte Indices, Male, medicine.medical_specialty, Erythrocytes, Cell, Alpha (ethology), alpha-haemoglobin pool, Enzyme-Linked Immunosorbent Assay, sickle cell anaemia, Anemia, Sickle Cell, Hydroxycarbamide, Hemoglobins, alpha haemoglobin-stabilising protein, Internal medicine, Gene expression, Genotype, medicine, Humans, Hydroxyurea, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Chemistry, hydroxycarbamide, Blood Proteins, Hematology, Middle Aged, Prognosis, Peptide Fragments, Red blood cell, Endocrinology, medicine.anatomical_structure, Case-Control Studies, Biomarker (medicine), Female, ELISA, Protein concentration, Biomarkers, Molecular Chaperones, medicine.drug
Abstract: International audience; Alpha haemoglobin-stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme-linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α-haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases.
Published: 2022

9. Acquired Spherocytosis Due to Somatic ANK1 Mutations as a Manifestation of Clonal Hematopoiesis in Elderly Patients

Author: Lamisse Mansour‐Hendili, Edouard Flamarion, Marc Michel, Caroline Morbieu, Christine Gameiro, Ivan Sloma, Bouchra Badaoui, Luc Darnige, Marion Camard, Ariane Lunati‐Rozie, Abdelrazak Aissat, Sihem Tarfi, Chloé Friedrich, Véronique Picard, Loïc Garçon, Nasséra Abermil, Sophie Kaltenbach, Isabelle Radford‐Weiss, Olivier Kosmider, Pascale Fanen, Pablo Bartolucci, Bertrand Godeau, Frédéric Galactéros, Benoît Funalot, Hôpital Henri Mondor, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Laboratoire d'Hématologie et d'Immunologie [CHU Henri Mondor], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), GHU AP-HP Centre Université de Paris, Université Paris Cité (UPCité), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Université Sorbonne Paris Cité (USPC), IMRB - GEIC2O/'Genetic and Environmental Interactions in COPD, Cystic fibrosis and Other (rare) respiratory diseases' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité des Maladies Génétiques du Globule Rouge [CHU Mondor], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Ankyrins, Mutation, Humans, Spherocytosis, Hereditary, Hematology, Clonal Hematopoiesis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged, Hematopoiesis
Abstract: International audience
Published: 2022

10. New approach to develop functionalized polyelectrolyte tube using bacteria as template

Author: Sabrina Belbekhouche, André Pawlak, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC)
Subjects: Polymers and Plastics, biology, Chemistry, Layer by layer, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, biology.organism_classification, medicine.disease_cause, 01 natural sciences, Polyelectrolyte, 0104 chemical sciences, Surfaces, Coatings and Films, Chemical engineering, Materials Chemistry, medicine, [CHIM]Chemical Sciences, Tube (fluid conveyance), 0210 nano-technology, Escherichia coli, Bacteria, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

11. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Author: Goubet, Anne-Gaëlle, Dubuisson, Agathe, Geraud, Arthur, Danlos, François-Xavier, Terrisse, Safae, Silva, Carolina Alves Costa, Drubay, Damien, Touri, Lea, Picard, Marion, Mazzenga, Marine, Silvin, Aymeric, Dunsmore, Garett, Haddad, Yacine, Pizzato, Eugenie, Ly, Pierre, Flament, Caroline, Melenotte, Cléa, Solary, Eric, Fontenay, Michaela, Garcia, Gabriel, Balleyguier, Corinne, Lassau, Nathalie, Maeurer, Markus, Grajeda-Iglesias, Claudia, Nirmalathasan, Nitharsshini, Aprahamian, Fanny, Durand, Sylvère, Kepp, Oliver, Ferrere, Gladys, Thelemaque, Cassandra, Lahmar, Imran, Fahrner, Jean-Eudes, Meziani, Lydia, Ahmed-Belkacem, Abdelhakim, Saïdani, Nadia, La Scola, Bernard, Raoult, Didier, Gentile, Stéphanie, Cortaredona, Sébastien, Ippolito, Giuseppe, Lelouvier, Benjamin, Roulet, Alain, Andre, Fabrice, Barlesi, Fabrice, Soria, Jean-Charles, Pradon, Caroline, Gallois, Emmanuelle, Pommeret, Fanny, Colomba, Emeline, Ginhoux, Florent, Kazandjian, Suzanne, Elkrief, Arielle, Routy, Bertrand, Miyara, Makoto, Gorochov, Guy, Deutsch, Eric, Albiges, Laurence, Stoclin, Annabelle, Gachot, Bertrand, Florin, Anne, Merad, Mansouria, Scotte, Florian, Assaad, Souad, Kroemer, Guido, Blay, Jean-Yves, Marabelle, Aurélien, Griscelli, Frank, Zitvogel, Laurence, Derosa, Lisa, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Champalimaud Centre for the Unknown [Lisbon], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Vaiomer, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), E-institute of Shanghai University Immunology Division, Shanghai University, Duke-NUS Medical School [Singapore], McGill University Health Center [Montreal] (MUHC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UNICANCER, Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Infrastructure INGESTEM, Université Paris Sud, A-GG was supported by Fondation pour la Recherche Médicale (FRM). LD has received support by the Philanthropia Fondation Gustave Roussy. The Gustave Roussy sponsored clinical study on COVID-19 (ONCOVID, NCT NCT04341207 has been supported by the Fondation Gustave Roussy, the Dassault family, Malakoff Humanis, Agnès b., Izipizi, Ralph Lauren and Sanofi). LZ and GK were supported by RHU Torino Lumière (ANR-16-RHUS-0008), ONCOBIOME H2020 network, the Seerave Foundation, the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR)—Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, FRM, a donation by Elior, the European Research Council (ERC), Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), CARE network (directed by Prof. Mariette, Kremlin Bicêtre AP-HP), and the SIRIC Cancer Research and Personalized Medicine (CARPEM). GI was supported by Italian Ministry of Health (grants Ricerca CorrenteLinea 1, 1 'Infezioni Emergenti e Riemergenti', projects COVID-2020-12371675 and COVID‐2020‐12371817). MMy and GG were supported by ANR Flash COVID-19 program and ARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs (PI: GG)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, École pratique des hautes études (EPHE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, LUMIERE - - LUMIERE2016 - ANR-16-RHUS-0008 - RHUS - VALID, European Union’s Horizon 2020 research and innovation programme under grant agreement. - ONCOBIOME - 825410 - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Oncostat team [Villejuif], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris (UP), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Université Paris Cité (UPC)
Subjects: Adult, DNA, Bacterial, Male, Time Factors, Adolescent, Article, Cohort Studies, Young Adult, Prognostic markers, Medical research, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphopenia, Nasopharynx, Neoplasms, Humans, Pandemics, Aged, Aged, 80 and over, SARS-CoV-2, COVID-19, Middle Aged, Prognosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virus Shedding, Interferon Type I, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Micrococcaceae
Abstract: International audience; Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B + FasL + , Eomes high TCF-1 high , PD-1 + CD8 + Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Published: 2021

12. Ex Vivo Activation of Red Blood Cell Senescence by Plasma from Sickle-Cell Disease Patients: Correlation between Markers and Adhesion Consequences during Acute Disease Events

Author: Philippe Chadebech, Corinne Vasseur, Pablo Bartolucci, Alicia Jouard, Gaetana Di Liberto, Gwellaouen Bodivit, Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité des Maladies Génétiques du Globule Rouge [CHU Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and CHADEBECH, Philippe
Subjects: 0301 basic medicine, Male, Blood transfusion, Erythrocytes, medicine.medical_treatment, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 030204 cardiovascular system & hematology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Biochemistry, Plasma, 0302 clinical medicine, Annexin, hemic and lymphatic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cellular Senescence, sickle-cell disease, hemic and immune systems, QR1-502, 3. Good health, medicine.anatomical_structure, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Acute Disease, Female, Erythrocyte Transfusion, hydration, circulatory and respiratory physiology, Senescence, Adult, phosphatidylserine, Context (language use), Anemia, Sickle Cell, Microbiology, Article, 03 medical and health sciences, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cell Adhesion, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, transfusion, Thrombospondin, business.industry, PIEZO1, Red blood cell, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, RBC’ senescence, Immunology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Ex vivo
Abstract: BACKGROUND: Blood transfusion remains a key treatment for managing occlusive episodes and painful crises in sickle-cell disease (SCD). In that clinical context, red blood cells (RBCs) from donors and transfused to patients, may be affected by plasma components in the recipients’ blood. Senescence lesion markers appear on the red cells after transfusion, shortening the RBC lifespan in circulation. In the specific context of SCD, senescence signals can also trigger the occlusive painful events, typical of the disease. This work follows through our previous data that described a RBC senescence process, rapidly detected after challenge with SCD pathological plasmas. In this clinical context, we wanted here to further explore the characteristics and physiologic consequences of AA RBC lesions associated with senescence, as lesions caused by RBCs after transfusion may have adverse consequences for SCD patients. METHODS: Plasma samples from SCD patients, with acute symptoms (n = 20) or steady-state disease (n = 34) were co-incubated with donor AA RBCs from blood units for 24 to 48 h. Specific markers signing RBC senescence were quantified after the incubation with SCD plasma samples. The physiologic in-flow adhesion was investigated on senescent RBCs, an in vitro technic into biochips that mimic adherence of RBCs during the occlusive events of SCD. RESULTS: Senescence markers on AA RBCs, together with their in-flow adhesion to the plasma-bridging protein thrombospondin, were associated with the clinical status of the SCD patients from whom plasma was obtained. In these experiments, the highest values were obtained for SCD acute plasma samples. Adhesion of senescent RBCs into biochips, which is not reversed by a pre-treatment with recombinant Annexin V, can be reproduced with the use of chemical agents acting on RBC membrane channels that regulate either Ca2+ entry or modulating RBC hydration. CONCLUSION: We found that markers on red cells are correlated, and that the senescence induced by SCD plasma provokes the adhesion of RBCs to the vessel wall protein thrombospondin. In-flow adhesion of senescent red cells after plasma co-incubations can be reproduced with the use of modulators of RBC membrane channels, activating the Piezo1 Ca2+ mechanosensitive channel provokes RBC adhesion of normal (non-senescent) RBCs, while blocking the Ca2+-dependent K+ Gardos channel, can reverse it. Clinically modulating the RBC adhesion to vascular wall proteins might be a promising avenue for the treatment of painful occlusive events in SCD.
Published: 2021

13. A Review of the Literature Organized Into a New Database: RHeference

Author: Aline Floch, Stéphane Téletchéa, Christophe Tournamille, Alexandre G. de Brevern, France Pirenne, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Créteil], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Université des Antilles (UA), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), and TOURNAMILLE, Christophe
Subjects: Databases, Factual, Computer science, Clinical Biochemistry, Data loss, 030204 cardiovascular system & hematology, computer.software_genre, Set (abstract data type), Database, 03 medical and health sciences, 0302 clinical medicine, RH blood group, Immunogenetics, Humans, Architecture, Alleles, Complement (set theory), Rh-Hr Blood-Group System, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Biochemistry (medical), Hematology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Data access, Phenotype, Blood Group Antigens, Data architecture, computer, 030215 immunology, RHD gene
Abstract: International audience; Hundreds of articles containing heterogeneous data describe D variants or add to the knowledge of known alleles. Data can be difficult to find despite existing online blood group resources and genetic and literature databases. We have developed a modern, elaborate database for D variants, thanks to an extensive literature search with meticulous curation of 387 peer-reviewed articles and 80 abstracts from major conferences and other sources. RHeference contains entries for 710 RHD alleles, 11 RHCE alleles, 30 phenotype descriptions (preventing data loss from historical sources), 35 partly characterized alleles, 3 haplotypes, and 16 miscellaneous entries. The entries include molecular, phenotypic, serological, alloimmunization, haplotype, geographical, and other data, detailed for each source. The main characteristics are summarized for each entry. The sources for all information are included and easily accessible through doi and PMID links. Overall, the database contains more than 10,000 individual pieces of data. We have set up the database architecture based on our previous expertise on database setup and biocuration for other topics, using modern technologies such as the Django framework, BioPython, Bootstrap, and Jquery. This architecture allows an easy access to data and enables simple and complex queries: combining multiple mutations, keywords, or any of the characteristics included in the database. RHeference provides a complement to existing resources and will continue to grow as our knowledge expands and new articles are published. The database url is http://www.rheference.org/.
Published: 2021

14. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author: Mickaël M. Ménager, Marine Luka, Marc Michel, Sophie Hue, Slim Fourati, Aurélien Sokal, Simon Fillatreau, Claude-Agnès Reynaud, Giovanna Barba-Spaeth, Annalisa Meola, Laetitia Languille, Jean-Michel Pawlotsky, Matthieu Mahévas, Jérôme Mégret, Félix A. Rey, Etienne Crickx, Asma Beldi-Ferchiou, Magali Bouvier-Alias, Jean-Claude Weill, Imane Azzaoui, Alexis Vandenberghe, Pascal Chappert, Samia Baloul, Anaïs Roeser, Ignacio Fernandez, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Inovarion, Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie, virologie, hygiène [Mondor], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Vaccine Research Institute (VRI), Physiopathologie et immunothérapies dans l’infection VIH [Créteil] (Inserm U955 Équipe 16), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This work was supported by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2), by the Fondation Princesse Grace, and, in part by an ERC Advanced Investigator Grant (B-response). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. A.S. was supported by a Poste d’Accueil from Inserm, A.R. by an Année Recherche from AP-HP and by a SNFMI fellowship., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute [Créteil, France] (VRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Adult, Somatic cell, Cell, Somatic hypermutation, Context (language use), Biology, Lymphocyte Activation, spike protein, Severity of Illness Index, Article, General Biochemistry, Genetics and Molecular Biology, plasma cells, RBD, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, medicine, Humans, neutralizing antibodies, Memory B cell, B cell, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, Germinal center, COVID-19, OC43, Middle Aged, Flow Cytometry, 3. Good health, somatic hypermutation, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, germinal center, Spike Glycoprotein, Coronavirus, Immunology, extrafollicular response, Single-Cell Analysis, HKU1, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection., Graphical abstract, The B cell response against SARS-CoV-2 shows a temporal shift from an extrafollicular reaction that includes memory B cells against seasonal coronaviruses toward a germinal center-dependent memory response encoding (spike-specific) neutralizing antibodies.
Published: 2021

15. Rapid Gardos Hereditary Xerocytosis Diagnosis in 8 Families Using Reticulocyte Indices

Author: Véronique Picard, Corinne Guitton, Lamisse Mansour-Hendili, Bernard Jondeau, Laurence Bendélac, Maha Denguir, Julien Demagny, Valérie Proulle, Frédéric Galactéros, Loic Garçon, DESSAIVRE, Louise, Université Paris-Saclay, Service d'Hématologie biologique [AP-HP Hôpital Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris Sud-Paris Saclay, Service de Pédiatrie Générale [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Henri Mondor, Hôpital Bicêtre, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Sud-Paris Saclay-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Laboratoire d'Hématologie [CHU Amiens]
Subjects: medicine.medical_specialty, red cell indices, reticulocytes, Physiology, [SDV]Life Sciences [q-bio], Hereditary Hemolytic Anemia, lcsh:Physiology, Reticulocyte Mean Corpuscular Volume, KCNN4, Gardos, Reticulocyte, Physiology (medical), Internal medicine, medicine, xerocytosis, lcsh:QP1-981, Mean corpuscular hemoglobin concentration, medicine.diagnostic_test, business.industry, RED-CELL INDICES, Brief Research Report, Piezo1, [SDV] Life Sciences [q-bio], Red blood cell, medicine.anatomical_structure, Endocrinology, business, Stomatocytosis
Abstract: Gardos channelopathy (Gardos-HX) or type 2 stomatocytosis/xerocytosis is a hereditary hemolytic anemia due to mutations in the KCNN4 gene. It is rarer than inherited type 1 xerocytosis due to PIEZO1 mutations (Piezo1-HX) and its diagnosis is difficult given the absence of a specific clinical or biological phenotype. We report here that this diagnosis can be sped up using red blood cell (RBC) indices performed on an ADVIA 2120 (Siemens®) analyzer, which measures reticulocyte mean corpuscular volume (rMCV) and mean corpuscular hemoglobin concentration (rMCHC). We studied reticulocyte indices in 3 new and 12 described patients (8 families) with Gardos-HX, 11 subjects presented the recurrent p.Arg352His mutation, 4 cases (two families) carried a private KCNN4 mutation. They were compared to 79 described patients (49 families) with Piezo1-HX. Surprisingly, in Gardos-HX cases, rMCV revealed to be smaller than MCV and rMCHC higher than MCHC, in contrast with normal or Piezo1-HX RBC. Consequently, ΔMCV (rMCV-MCV) was −0.9 ± 5 fL vs. 19.8 ± 3 fL (p < 0.001) in Gardos compared with Piezo1-HX and ΔMCHC (rMCHC-MCHC) was 18.7 ± 13 vs. −50 ± 8.7 g/L (p < 0.001). A threshold of 8.6 fL for ΔMCV and −5.5 g/L for ΔMCHC could discriminate between Gardos and Piezo1-HX with 100% sensitivity and specificity, regardless of age, mutation or splenectomy status. Consequently, we showed that reticulocytes indices are useful to suggest Gardos-HX on blood count results, allowing to rapidly target these patients for gene analysis. In addition, these parameters may prove useful as a ‘functional tool’ in interpreting new KCNN4 variants.
Published: 2021

16. The Enigmatic Emerging Role of the C-Maf Inducing Protein in Cancer

Author: Dil Sahali, Mario Ollero, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Ollero, Mario, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: 0301 basic medicine, T cell, [SDV]Life Sciences [q-bio], Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Biology, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Adverse effect, Kidney, lcsh:R5-920, Cancer, solid tumors, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, antiangiogenic therapy, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, idiopathic nephrotic syndrome, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Medicine (General), Nephrotic syndrome, Tyrosine kinase
Abstract: International audience; The C-Maf-Inducing protein (CMIP) was first described as overexpressed in T cell subpopulations of idiopathic nephrotic syndrome (INS) patients. Later, it was found concomitantly upregulated in podocytes. CMIP expression has also been reported in several types of cancer, including blood malignancies and solid tumors, in many cases accompanied by nephrotic syndrome. In addition to these observations, the duality of CMIP overexpression in the kidney and INS lesions, has been extensively reported as one of the adverse effects of anticancer therapy based on anti-receptor tyrosine kinase drugs. As a consequence, a growing body of evidence points at CMIP as playing a role in cancer. This includes its reciprocal regulatory ties with NF-κB and WT1, and the more recent reports showing an involvement in regulatory circuits in cancer cells. The ensemble of the current information justifies to propose CMIP as an important piece of the puzzle of biological systems involved in cancer and other diseases and its potential as a target.
Published: 2021

17. RHCE01 48G>C, 366del allele with silencedRHCEce expression

Author: Barrault, Aurélie, Floch, Aline, Devaux, Laurent, Gaillard, Kévin, Muralitharan, Vintuya, Pirenne, France, Tournamille, Christophe, TOURNAMILLE, Christophe, Etablissement Français du Sang [Créteil], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Rh-Hr Blood-Group System, Base Sequence, [SDV]Life Sciences [q-bio], Exons, Hemagglutination Tests, Real-Time Polymerase Chain Reaction, [SDV] Life Sciences [q-bio], Blood Grouping and Crossmatching, Codon, Nonsense, Pregnancy, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Point Mutation, Female, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Frameshift Mutation, Alleles, ComputingMilieux_MISCELLANEOUS, Sequence Deletion
Abstract: International audience; No abstract available
Published: 2021

18. Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Author: Martin Martinot, Aude Jary, Samira Fafi-Kremer, Valentin Leducq, Heloise Delagreverie, Marc Garnier, Jérôme Pacanowski, Arsène Mékinian, France Pirenne, Pierre Tiberghien, Vincent Calvez, Catherine Humbrecht, Anne-Geneviève Marcelin, Karine Lacombe, Hôpitaux Civils de Colmar, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Strasbourg], Groupe de recherche clinique en anesthésie réanimation médecine périopératoire [CHU Pitié-Salpétrière] (GRC ARPE), Département Médico-Universitaire réanimation anesthésie médecine péri-opératoire [Sorbonne Université] (DMU DREAM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Microbiology (medical), Adenosine monophosphate, Coronavirus disease 2019 (COVID-19), viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, RNA-dependent RNA polymerase, Viremia, medicine.disease_cause, Virus, 03 medical and health sciences, chemistry.chemical_compound, medicine, B cell, Immunodeficiency, Mutation, business.industry, virus diseases, medicine.disease, Virology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, chemistry, business
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.
Published: 2021

19. Thrombopénie immunologique : de la physiopathologie aux traitements

Author: Bernard Bonnotte, Matthieu Mahévas, Sylvain Audia, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Henri Mondor, and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Syk, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neonatal Fc receptor, hemic and lymphatic diseases, Internal Medicine, medicine, ComputingMilieux_MISCELLANEOUS, Autoimmune disease, biology, business.industry, Gastroenterology, Autoantibody, medicine.disease, 3. Good health, Immune thrombocytopenia, Treatment, [SDV] Life Sciences [q-bio], 030104 developmental biology, Immunology, biology.protein, Rituximab, Antibody, business, 030215 immunology, medicine.drug
Abstract: International audience; Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an immune peripheral destruction of platelets and an inappropriate platelet production. The pathogenesis of ITP is now better understood: it involves a humoral immune response which dependents on the stimulation of B cells by specific T cells called T follicular helper cells, leading to their differentiation into plasma cells that produce antiplatelet antibodies thus promoting the phagocytosis of platelets mainly by splenic macrophages. The deciphering of ITP pathogenesis has led to a better understanding of the inefficiency of treatments such as rituximab, although it has not provided yet the determination of biological predictive factor of response to treatments. Moreover, new therapeutic perspectives have been opened in the last few years with the development of molecules targeting Fcγ receptor signalling such as Syk inhibitor, or molecules increasing the clearance of pathogenic autoantibodies such as inhibitors of the neonatal Fc receptor (FcRn).
Published: 2021

20. De Novo Focal and Segmental Glomerulosclerosis After COVID-19 in a Patient With a Transplanted Kidney From a Donor With a High-risk APOL1 Variant

Author: Aude Mausoleo, Marie Matignon, Julie Oniszczuk, Stephanie Malard-Castagnet, Anna Boueilh, Thomas Stehlé, David Buob, Marie Christine Verpont, Dil Sahali, Philippe Grimbert, Anissa Moktefi, Vincent Audard, Slim Fourati, Nicolas Pallet, Khalil El Karoui, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), service Anatomie et Cytologie Pathologique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Etablissement Français du Sang [Nantes], Department of Pathology [Cleveland, OH, USA] (School of Medicine), Case Western Reserve University [Cleveland], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor - Service de néphrologie et transplantation, Service de Néphrologie-Transplantation [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: Male, Pathology, medicine.medical_specialty, Apolipoprotein L1, [SDV]Life Sciences [q-bio], Context (language use), 030230 surgery, Kidney, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Genotype, medicine, Humans, Genotyping, ComputingMilieux_MISCELLANEOUS, Transplantation, biology, medicine.diagnostic_test, Glomerulosclerosis, Focal Segmental, SARS-CoV-2, business.industry, Not Otherwise Specified, COVID-19, Glomerulosclerosis, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, 3. Good health, biology.protein, 030211 gastroenterology & hepatology, Renal biopsy, business, Nephrotic syndrome
Abstract: There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined.We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury.Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype.In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.
Published: 2020
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21. Comparison of Plasma Clearance With Early-Compartment Correction Equations and Urinary Clearance in High GFR Ranges

Author: Dominique Prié, Martin Flamant, Hans Pottel, Pierre Delanaye, Christine A. White, Gunnar Sterner, Sandrine Lemoine, Vincent Audard, Thomas Stehle, François Gaillard, Laurence Dubourg, Etienne Cavalier, Marie Courbebaisse, Emmanuelle Vidal-Petiot, Université de Liège, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor - Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Skane University Hospital [Malmo], Lund University [Lund], Queen's University [Kingston, Canada], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), KU Leuven Campus Kulak Kortrijk [Belgium], CarMeN, laboratoire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: medicine.medical_specialty, PREDICTION, Urinary system, IOTHALAMATE, [SDV]Life Sciences [q-bio], Inulin, 030232 urology & nephrology, Urology, Renal function, 51cr edta, 030204 cardiovascular system & hematology, Cr-51-EDTA, GLOMERULAR-FILTRATION-RATE, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Clinical Research, SURFACE AREA NORMALIZATION, IOHEXOL, medicine, In patient, 51Cr-EDTA, Plasma clearance, glomerular filtration rate, Science & Technology, inulin, business.industry, ADULTS, Urology & Nephrology, PERFORMANCE, Diseases of the genitourinary system. Urology, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, Nephrology, CLINICAL-PRACTICE, RC870-923, iohexol, Iohexol, business, CONCORDANCE, Life Sciences & Biomedicine, medicine.drug
Abstract: Introduction Glomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay—corresponding to the distribution of the tracer—using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min per 1.73 m2, and their respective performances against a reference, urinary GFR measurement are unclear. Methods In patients with mGFR >90 ml/min per 1.73 m2 from 6 different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51Cr-ethylenediamine tetraacetic acid (EDTA), after correction using Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin. Results In 438 participants (median age 41 [39–42] years, 43% women), the median urinary clearance was 100.8 (94.7–112.6) ml/min per 1.73 m2. Plasma clearances using the correction equations were 105.7 (96.8–119.2), 102.4 (95.2–112.9), 100.7 (93.6–111.1), 102.6 (95.2–113.4), and 106.0 (98.2–117.6) ml/min per 1.73 m2 for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared with urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73%, 72%, and 71%, respectively, vs. 63% and 66% for C and N), whereas BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance >130 ml/min per 1.73 m2). Conclusion The BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range., Graphical abstract
Published: 2020

22. Gangliosides in Podocyte Biology and Disease

Author: Mario Ollero, Berkan Savas, Dil Sahali, Massimo Aureli, Giuseppe Astarita, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Georgetown University, University of Milan, Hôpital Henri Mondor - Service de néphrologie et transplantation, Université Paris Est Créteil, IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: 0301 basic medicine, Ceramide, kidney, [SDV]Life Sciences [q-bio], glomerulus, Review, Biology, glomerulopathies, Catalysis, Podocyte, rafts, lcsh:Chemistry, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glomerular Filtration Barrier, Gangliosides, medicine, Animals, Humans, ceramide, Physical and Theoretical Chemistry, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, chemistry.chemical_classification, podocytopathies, Ganglioside, glycosphingolipids, Podocytes, nephrotic syndrome, Organic Chemistry, Cell Membrane, General Medicine, Computer Science Applications, Sialic acid, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Enzyme, lcsh:Biology (General), lcsh:QD1-999, chemistry, 030220 oncology & carcinogenesis, Function (biology), Homeostasis
Abstract: International audience; Gangliosides constitute a subgroup of glycosphingolipids characterized by the presence of sialic acid residues in their structure. As constituents of cellular membranes, in particular of raft microdomains, they exert multiple functions, some of them capital in cell homeostasis. Their presence in cells is tightly regulated by a balanced expression and function of the enzymes responsible for their biosynthesis-ganglioside synthases-and their degradation-glycosidases-. Dysregulation of their abundance results in rare and common diseases. In this review we make a point on the relevance of gangliosides and some of their metabolic precursors, such as ceramides, in the function of podocytes, the main cellular component of the glomerular filtration barrier, as well as their implications in podocytopathies. The results presented in this review suggest the pertinence of clinical lipidomic studies targeting these metabolites.
Published: 2020

23. A sensitive S-Trap-based approach to the analysis of T cell lipid raft proteome

Author: Chhuon, Cerina, Zhang, Shao-Yu, Jung, Vincent, Lewandowski, Daniel, Lipecka, Joanna, Pawlak, Andre, Sahali, Dil, Ollero, Mario, Guerrera, Ida Chiara, Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Est Créteil, IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Recherche sur la Réparation et la Transcription dans les Cellules Souches (LRTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Université Paris Sud (Université Paris Sud), AP-HP, Groupe Henri-Mondor Albert-Chenevier, Service de Néphrologie, Université Paris-Est Créteil, Créteil, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Inserm U955, équipe 21, Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Canalopathies épithéliales: la mucoviscidose et autres maladies, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ollero, Mario
Subjects: lymphocytes, S-trap : Filter aided sample preparation, Proteome, detergent-free, T-Lymphocytes, [SDV]Life Sciences [q-bio], QD415-436, OptiPrep, Biochemistry, raftomics, immunology, Mice, FASP, tandem mass spectrometry, Methods, Animals, Humans, tandem mass-spectrometry, cell signaling, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, Mice, Inbred BALB C, LAT: linker for activation of T cells, TCR: T cell receptor immunology, detergentfree, Lipids, [SDV] Life Sciences [q-bio], HEK293 Cells, membranes, FASP : Filter aided sample preparation, lipids (amino acids, peptides, and proteins), Chromatography, Liquid
Abstract: International audience; The analysis of T cell lipid raft proteome is challenging due to the highly dynamic nature of rafts and the hydrophobic character of raft-resident proteins. We explored an innovative strategy for bottom-up lipid raftomics based on suspension trapping (S-trap) sample preparation. Mouse T cells were prepared from splenocytes by negative immunoselection and rafts were isolated by a detergent-free method and OptiPrep gradient ultracentrifugation. Microdomains enriched in Flotillin-1, LAT and cholesterol were subjected to proteomic analysis through an optimized protocol based on STrap and high pH fractionation, followed by nano-LC-MS/MS. Using this method, we identified 2680 proteins in the raft-rich fraction and established a database of 894 T cell raft proteins. We then performed a differential analysis on the raft-rich fraction from non-stimulated vs. anti-CD3/CD28 TCR-stimulated T cells. Our results revealed 42 proteins present in one condition and absent in the other. For the first time, we performed a proteomic analysis on rafts from ex-vivo T cells obtained from individual mice, before and after TCR activation. This work demonstrates that the proposed method utilizing an Strap based approach for sample preparation increases the specificity and sensitivity of lipid raftomics. Data are available via ProteomeXchange with identifier PXD016476.
Published: 2020

24. Anti-C5 antibody treatment for delayed hemolytic transfusion reactions in sickle cell disease

Author: null Aline Floch, null Alexandre Morel, null Fabian Zanchetta-Balint, null Catherine Cordonnier-Jourdin, null Slimane Allali, null Maximilien Grall, null Ghislaine Ithier, null Benjamin Carpentier, null Sadaf Pakdaman, null Jean-Claude Merle, null Radjiv Goulabchand, null Tackwa Khalifeh, null Ana Berceanu, null Cécile Helmer, null Christelle Chantalat-Auger, null Véronique Frémeaux-Bacchi, null Marc Michel, null Mariane de Montalembert, null Armand Mekontso-Dessap, null France Pirenne, null Anoosha Habibi, null Pablo Bartolucci, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC - Biotherapie - CHU Henri Mondor, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Inflammation, Case Reports, Anemia, Sickle Cell, 030204 cardiovascular system & hematology, Hemolysis, MESH: Anemia, Sickle Cell* / therapy, MESH: Transfusion Reaction, 03 medical and health sciences, Classical complement pathway, 0302 clinical medicine, Antigen, Isoantibodies, medicine, Humans, MESH: Humans, biology, business.industry, Transfusion Reaction, Transfusion medicine, Hematology, medicine.disease, MESH: Hemolysis, MESH: Isoantibodies, 3. Good health, Delayed hemolytic transfusion reaction, Immunology, Alternative complement pathway, biology.protein, medicine.symptom, Antibody, business, Packed red blood cells, 030215 immunology
Abstract: International audience; Delayed hemolytic transfusion reaction (DHTR) is an unpredictable severe complication of transfusion in patients with sickle cell disease (SCD). It presents clinically as a vaso-occlusive crisis (VOC), often associated with the failure of one or more organs, after the transfusion of packed red blood cells (pRBC).1,2 Hyperhemolysis is encountered in the most severe forms. Both transfused and autologous red blood cells (RBC) are lysed.The mechanisms underlying DHTR remain unclear. Alloantibodies against RBC antigens were initially thought to underlie the pathophysiology, but no such antibodies are detected in about a third of the cases.3RBC degradation products, such as hemoglobin and heme, are released into the bloodstream during intravascular hemolysis. These elements and heme-loaded membrane microvesicles have recently been implicated in inflammation and organ injury in DHTR.4 Complement is activated via the classical pathway, by alloantibodies, and/or via the alternative pathway, by free heme.5 Hemedependent complement deposits on the endothelium contribute to organ damage.6 Due to these vascular lesions, hyperhemolysis often progresses to multiple organ failure and, in some cases, death.
Published: 2020

25. Hydroxycarbamide decreases the free alpha‐hemoglobin pool in red blood cells of adult patients with sickle cell anemia

Author: Elisa Domingues-Hamdi, Anoosha Habibi, Véronique Baudin-Creuza, Pablo Bartolucci, Stéphane Moutereau, Corinne Vasseur, Frédéric Galactéros, Sadaf Pakdaman, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité, laboratory of Excellence GR-Ex, Paris, France, Etablissement Français du Sang (EFS), Créteil, France., Département de Biochimie-Biologie Moléculaire, Pharmacologie, Génétique Médicale [CHU Henri Mondor], CHU Henri Mondor, Unité des Maladies Génétiques du Globule Rouge [CHU Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and BAUDIN-CREUZA, Véronique
Subjects: 0303 health sciences, medicine.medical_specialty, Adult patients, business.industry, [SDV]Life Sciences [q-bio], Hematology, Alpha hemoglobin, medicine.disease, Gastroenterology, Sickle cell anemia, 3. Good health, [SDV] Life Sciences [q-bio], Hydroxycarbamide, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology, medicine.drug
Abstract: International audience; No abstract available
Published: 2020

26. New molecular basis associated with CD36 ‐negative phenotype in the sub‐Saharan African population

Author: Emilie Le Toriellec, Vintuya Muralitharan, Philippe Chadebech, Alicia Jouard, Hélène Ansart‐Pirenne, France Pirenne, Christophe Tournamille, Laure Croisille, Etablissement Français du Sang [Créteil], laboratory of Excellence GR-Ex, Paris, France, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and CHADEBECH, Philippe
Subjects: CD36 Antigens, medicine.drug_class, CD36, [SDV]Life Sciences [q-bio], Immunology, Anemia, Sickle Cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030204 cardiovascular system & hematology, Monoclonal antibody, Compound heterozygosity, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Antigen, INDEL Mutation, medicine, Immunology and Allergy, Humans, Child, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Africa South of the Sahara, [SDV.GEN]Life Sciences [q-bio]/Genetics, medicine.diagnostic_test, biology, Hematology, Exons, Phenotype, 3. Good health, [SDV] Life Sciences [q-bio], Red blood cell, medicine.anatomical_structure, biology.protein, Codon, Terminator, Female, Antibody, 030215 immunology
Abstract: International audience; Background: CD36 glycoprotein is expressed by various cell types, including platelets (PLTs), monocytes, and erythroid precursors, and is also the receptor for several ligands. However, absence of CD36 expression seems asymptomatic and is poorly described in Caucasians. In contrast, the frequency reaches 7% and 11% in African Caribbean and Asian persons, respectively. Lack of CD36 expression exposes to the risk of immunization in case of pregnancy or PLT transfusion. Two types of deficiency have been described: in Type I, PLTs and monocytes lack CD36 expression and the subjects are homozygous or compound heterozygous for CD36 mutations, whereas in Type II, only PLTs (Type IIa), and rarely also erythroid cells (Type IIb), are affected. Molecular events leading to Type II deficiency are poorly understood.Case report: An African girl, diagnosed with homozygous sickle cell disease and regularly transfused, was assessed for PLT CD36 expression by immunofluorescence microscopy. The deficiency was then confirmed by monoclonal antibody immobilization of PLT antigen (MAIPA) assay, and the subtype was assessed by flow cytometry. The underlying molecular basis was characterized by DNA sequencing. Furthermore, we tested the serum for possible anti-CD36 immunization.Results and conclusion: Flow cytometric analysis on the patient's blood samples allowed the diagnosis of Type I CD36 deficiency. CD36 antibodies, probably due to her past history of red blood cell transfusions, were identified by MAIPA and by Luminex technology assay. Interestingly, we identified through sequencing a new molecular basis involved in CD36 deficiency: two adenines were replaced by one guanine in Exon 4 (c.367_368delAAinsG) leading to a stop codon at Position 76.
Published: 2020

27. Hb Angers: A new α2-globin variant [α2 (140)(HC2) Tyr → Ser; HBA2: C.422 AC] with increased oxygen affinity leading to erythrocytosis

Author: Anne Peron, Serge Pissard, Henri Wajcman, Isabelle Peronet, Corentin Orvain, Laurent Kiger, Frédéric Galactéros, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Genotype, Thalassemia, Hemoglobins, Abnormal, Clinical Biochemistry, Increased oxygen affinity, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polycythemia, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, alpha-Globins, alpha-Thalassemia, medicine, Humans, Globin, ComputingMilieux_MISCELLANEOUS, Alleles, 030304 developmental biology, 0303 health sciences, Chemistry, Biochemistry (medical), Hematology, General Medicine, medicine.disease, Molecular biology, 3. Good health, Oxygen, Amino Acid Substitution, 030220 oncology & carcinogenesis, Mutation, Blood Gas Analysis, Protein Binding
Abstract: International audience
Published: 2020

28. CMIP is a negative regulator of T cell signaling

Author: André Pawlak, Vincent Frontera, Giuseppe Astarita, Julie Oniszczuk, Ida Chiara Guerrera, Etienne Cogné, Kelhia Sendeyo, Mario Ollero, P. Vachin, Carole Hénique, Cerina Chhuon, Berkan Savas, Dil Sahali, Vincent Audard, Université Paris Est Créteil, IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Department of Biochemistry and Molecular &Cellular Biology, Georgetown University, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Service de Néphrologie, Institut francilien de recherche en néphrologie et transplantation, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Proteomics, CD3 Complex, Autoimmune diseases, T-Lymphocytes, CD3, T cell, [SDV]Life Sciences [q-bio], Immunology, T cells, Translational immunology, Mice, Transgenic, Video microscopy, Proto-Oncogene Proteins c-fyn, Article, Glycosphingolipids, 03 medical and health sciences, Membrane Microdomains, 0302 clinical medicine, FYN, CD28 Antigens, medicine, Transgenic mice, Animals, Humans, Immunology and Allergy, Adaptor Proteins, Signal Transducing, 030304 developmental biology, 0303 health sciences, biology, Chemistry, T-cell receptor, Cell Polarity, CD28, CMIP, Cell biology, Enzyme Activation, Phenotype, src-Family Kinases, Infectious Diseases, medicine.anatomical_structure, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), 030220 oncology & carcinogenesis, biology.protein, Cytokines, Cell activation, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src
Abstract: Upon their interaction with cognate antigen, T cells integrate different extracellular and intracellular signals involving basal and induced protein-protein interactions, as well as the binding of proteins to lipids, which can lead to either cell activation or inhibition. Here, we show that the selective T cell expression of CMIP, a new adapter protein, by targeted transgenesis drives T cells toward a naïve phenotype. We found that CMIP inhibits activation of the Src kinases Fyn and Lck after CD3/CD28 costimulation and the subsequent localization of Fyn and Lck to LRs. Video microscopy analysis showed that CMIP blocks the recruitment of LAT and the lipid raft marker cholera toxin B at the site of TCR engagement. Proteomic analysis identified several protein clusters differentially modulated by CMIP and, notably, Cofilin-1, which is inactivated in CMIP-expressing T cells. Moreover, transgenic T cells exhibited the downregulation of GM3 synthase, a key enzyme involved in the biosynthesis of gangliosides. These results suggest that CMIP negatively impacts proximal signaling and cytoskeletal rearrangement and defines a new mechanism for the negative regulation of T cells that could be a therapeutic target.
Published: 2020

29. Impact of renal function on hydroxyurea exposure in sickle-cell disease patients

Author: Claire Pressiat, Pablo Bartolucci, Anne Hulin, Frédéric Galactéros, Vincent Audard, Thomas Stehlé, Marie-Georgine Rakotoson, Caroline Barau, Raphaele Arrouasse, Anoosha Habibi, CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), EFS Ile de France, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), laboratory of Excellence GR-Ex, Paris, France, Unité des maladies génétiques du globule rouge (UPEC - Hôpital Henri Mondor AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre de référence des syndromes drépanocytaires majeurs, APHP Henri Mondor, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité des Maladies Génétiques du Globule Rouge [CHU Mondor], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Urinary system, Population, Urology, Renal function, Urine, Anemia, Sickle Cell, Kidney, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Antisickling Agents, Medicine, Humans, Hydroxyurea, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, education, ComputingMilieux_MISCELLANEOUS, Pharmacology, education.field_of_study, business.industry, Area under the curve, medicine.disease, business, Glomerular hyperfiltration, Kidney disease
Abstract: Aims This prospective study aimed to develop a population pharmacokinetics (PK) model of hydroxyurea (HU) in patients with sickle cell disease. This model can be used to determine the impact of glomerular filtration rate (GFR) on HU kinetics. Methods We included 30 patients. They underwent HU pharmacokinetics analyses of plasma and urine. Six underwent PK analyses in 2 periods with and without angiotensin-converting enzyme inhibitor. HU was assayed with a validated high-performance liquid chromatography-UV method. Noncompartmental PK analysis was conducted and a population PK model built with Monolix. This model was validated externally on another 56 patients. HU PK was simulated as a function of GFR. Results The HU PK model was constructed as a 2-compartment model with first-order absorption and elimination. The quality criteria were good, including for external validation. We found that estimated GFR (eGFR) and body weight affected HU PK, with lower eGFR or body weight associated with a higher HU area under the curve. We recommend the monitoring of HU through eGFR and body weight, which together account for 47% of its variability. Urinary HU fractions and renal clearance were higher in the glomerular hyperfiltration group and lower in the moderate chronic kidney disease group, respectively. No differences in nonrenal HU clearance were observed. Conclusion Estimated GFR has an impact on the kinetics of hydroxyurea, and HU dose should be adapted accordingly. Angiotensin-converting enzyme inhibitor seems to have minor effect on HU PK in adults with sickle cell disease.
Published: 2020

30. Imported Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis

Author: Amoura, Ariane, Moktefi, Anissa, Halfon, Matthieu, Karras, Alexandre, Rafat, Cédric, Gibier, Jean-Baptiste, Gleeson, Patrick, Servais, Aude, Argy, Nicolas, Maillé, Pascale, Belenfant, Xavier, Gueutin, Victor, Delpierre, Alexia, Tricot, Leila, El Karoui, Khalil, Jourde-Chiche, Noémie, Houze, Sandrine, Sahali, Dil, Audard, Vincent, service Anatomie et Cytologie Pathologique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'anatomopathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor - Service de néphrologie et transplantation, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

31. Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Author: Victor Judith, Devaux Mathilde, Corre Clémence, Morin Franck, Ebstein Esther, Desmurs Marie, Juillard Laurent, Descamps Elise, Galland Joris, Gahier Penhoat Mélanie, Hellier Jean-Pierre, Mariette Xavier, Poix Elsa, Hudry Christophe, Constant Elodie, Trijau Sophie, Moranne Olivier, Diot Elisabeth, Hie Miguel, Guilpain Philippe, Boussoualim Karima, Mathian Alexis, Pouchot Jacques, Rohmer Julien, Senet Patricia, Michaud Martin, Tieulie Nathalie, Liote Frédéric, Ducornet Angélique, Couret Marie, Revuz Sabine, Morel Hugo, Moly Marie, Direz Guillaume, Milesi-Lecat Anne-Marie, Meinzer Ulrich, Bader-Meunier Brigitte, Steib Sarah, Gauthier-Prieur Maud, Bertolini Ewa, Gombert Bruno, Dumel Anne-Elisabeth, Henriot Basile, Froissart Antoine, Smets Perrine, Robin Sophie, Rousselin Clémentine, Moulinier Laurence, Mazet-Guillaume Betty, Brondino Regine, Malochet-Guinamand Sandrine, Balandraud Nathalie, Gibert Christelle, Godeau Bertrand, Aeschlimann Florence, Bonnet Christine, Plassard Samira, Lebrun Agnès, Mehsen-Cetre Nadia, Arlet Jean-Benoît, Gagneux-Lemoussu Laurence, Kemiche Farid, Michon Mathilde, Szafors Paulina, Werle Claude, Guillaud Constance, La Batide Alanore Sylvain, Borie Raphaël, Chazerain Pascal, Puyraimond-Zemmour Déborah, Barrelet Audre, Bach-Bunner Maxime, Flaisler Françoise, Euvrard Romain, Evon Philippe, Feurer Elodie, Gerard Nathalie, Gervais Elisabeth, Sordet Christelle, Bally Stéphane, Mazouyez Arnaud Angers, Guillot Xavier, Comarmond Chloé, Leloire Olivier, Fauconier Marion, Bouhour Françoise, Woessner Juliette, Jaccard Clara, Langlois Vincent, Sicaud Aurélie, Rolland Michel, Kabala Anna, Atlan Lucie, Amador-Borreiro Blanca, Jan Catherine, Leturcq Tifenn, Gonnet-Gracia Camille, Lanot Sylvain, Hachulla Eric, Bonidan Olivier, Domont Fanny, Dumaine Cécile, Bouiller Kévin, Senbel Eric, Comparon Céline, Huguenel Serge, Despaux Jacques, Roth Olivier, Berthoux Emilie, Dehimat Sarahe, Costedoat-Chalumeau Nathalie, Bayer Guillaume, Melki Isabelle, Toussirot Eric, Buchlin Pierre, Baumier Vincent, Charcot Agnès, Durand Géraldine, Garraud Thomas, Richez Christophe, Gillard Jérôme, Chaigne Benjamin, Rousiere Mickaël, Le Guen Guegan Sophie, Chertok Pascale, Lucas Virginie, Sadji Fatiha, Garnier Nicole, Sailler Laurent, Garrot Jean-François, Taffignon-Clave Séverine, Charles Pierre, Bernoux-Manat Brigitte, Salliot Carine, Fechtenbaum Jacques, Quenet Marion, Le Guenno Guillaume, Lanteri Aurélia, Hermet Marion, Delahousse Michel, Basch André, Grateau Gilles, Chevalier Xavier, Nocturne Gaétane, Schmidt Jean, Pacaud-Vitoux Isabelle, Roumier Mathilde, Rozenberg Sylvie, Veillard Eric, Roux Nicolas, Marhadour Thierry, Colette-Cedoz Marie-Eve, Cohen Gregory, Foltz Violaine, Fouque-Aubert Anne, Havard Marie-Noelle, Molto Anna, Chevreau Maxime, Strotz Victor, Allanore Yannick, Grardel Bruno, Francois-Pradier Hélène, Devauchelle-Pensec Valérie, Hennequin Pascal, Warzocha Ursula, Collercandy Nived, Bayle Sophie, Audren Victor, Virone Alexandre, Bennet Pascal, Grados Franck, Charpin Caroline, Fuzibet Piera, Albert Jean-David, Larbre Jean-Paul, Coutarel Cécile, Nicolas-Vullierme Sabine, Gastaldi Romain, Guyot Marie-Hélène, Georgescu Dana, Clavel Gaëlle, Tison Alice, Viallard Jean-François, Maria Alexandre, Glanowski Camille, Leroux Christophe, Vidon Mathias, Banal Frédéric, Fulpin Jean, Chotard Emilie, Gaud-Listrat Véronique, Jean Sylvie, Seguier Julie, Jacquemier Jean-Michel, Chatelus Emmanuel, Djeddi Djamal-Dine, Contamine-Sur-Arve Mazyad Hassan, Georgin-Lavialle Sophie, Belot Alexandre, Seve Pascal, Willems Alexandra, Moulis Guillaume, Latourte Augustin, Roux Marielle, Bolla Gilles, Renard Myriam, Xerri-Campano Bernadette, Bisson-Vaivre Aurélia, Fichet Amandine, Dufauret-Lombard Carine, Nielly Hubert, Ledoult Emmanuel, Alcais Didier, Giraudet-Le Quintrec Jeanine-Sophie, Wendling Daniel, Govindaraju-Audouard Sophie, Claudepierre Pascal, Fritz Pierre, Fougerousse Anne-Claire, Marotte Hubert, Fabre Sylvie, Banneville Béatrice, Quartier-Dit-Maire Pierre, Juge Pierre-Antoine, Moura Bertrand, Maillet Thibault, Messer Laurent, Thomachot Benoît, Giraud-Morelet Aude, Sparsa Lætitia, Kabchou Abdelkrim, Grasland Anne, Maurier François, Belin Véronique, Grenoble Gimonnet Pauline, Balblanc Jean-Charles, Andre Emma, Veillard Ericveillard Marie-Eliseeric, Chu Miow Lin, Pugnet Grégory, Wisniewski Michel, Carbasse Aurélia, Rene Jessica, Economu-Dubosc Andra, Bouldoires Bastien, Glace Baptiste, Benhamou Mathilde, Legoupil Nathalie, Morel Jacques, Castel Brice, Lafforgue Pierre, Carteni Maurizio, Lohse Anne, Detree Frédérick, Celant Annalisa, Trefond Ludovic, Maillard Hélène, Remy Philippe, Barnetche Thomas, Servettaz Amélie, Vigne Camille, Ferreira-Maldent Nicole, Mangon Quentin, Keraen Jérémy, Fautrel Bruno, Frantzen Léa, Legrand Erick, Sellam Jérémie, Tenenbaum Nora, Sene Thomas, Duc Catherine, Bouvard Eric, Dieudonne Yannick, Ollagnon Henri-Olivier, Deslandre Chantal, Gury Aline, Desplats Marie, Karman Françoise, Drouet Béatrice, Vidon Claire, Kone-Paut Isabelle, Groza Monica, Jamard Bénédicte, Parrot Antoine, Vial Guillaume, Ebbo Mikaël, Ait-Abdallah Nassim, Veillon Laurent, Roriz Mélanie, Chaillous Benoît, Rouidi Sid-Ahmed, Sobanski Vincent, Poulet Antoine, Clavel-Osorio Cyril, Nguyen Minh, Felten Renaud, Goulenok Tiphaine, Audoin-Pajot Christine, Foret Jennifer, Arniaud Denis, Benammar Mohammed, Boudou Laurence, Pascaud-Mansour Yasmina, Pavy Stephan, Sornay-Rendu Elisabeth, Pascart Tristan, Madelon Aurélie, Koreichi Abdeldajallil, Flipo René-Marc, El Mahou Soumaya, Benmansour Ahmed, Arty-Hue Herliette, Pers Yves-Marie, Hittinger-Roux Ambre, Sacco Isabelle, Fernandes Fanny, Gandjbakhch Frédérique, Maury Frédéric, Hacquard-Bouder Cécile, Foutrier-Morello Catherine, Rossi Linda, Belkhir Rakiba, Riviere Etienne, Drumez Elodie, Avouac Jérôme, Benainous Ruben, Champy Romuald, Florens Nans, Pichon Maud, Gibert Eric, Benhamou Ygal, Portier Agnès, Riviere Sébastien, Pham Thao, Blaison Gilles, Colombey Antoine, Marchou-Lopez Sylvie, Roux Fabienne, Leroy Rémi, Lejeune Charlotte, Bacquet-Deschryver Hélène, Romier Mélanie, Simoens Justine, Caumont Hervé, Arnaud Laurent, Paulin Lætitia, Duret Pierre-Marie, Dieude Philippe, Coury-Lucas Fabienne, Pha Micheline, Herasse Muriel, Mahevas Matthieu, Roitg Isabelle, Karkowski Ludovic, Dhote Robin, Chaudier Bernard, Gourmelen Olivier, Trouillier Sébastien, Henry Julien, Daver-Malaterre Laurence, Cathebras Pascal, Goupille Philippe, Seror Raphaële, Thomas Thierry, Pertuiset Edouard, Amoura Zahir, Richard-Colmant Gaëlle, Souchaud-Debouverie Odile, Lahalle Sophie, Jouvray Mathieu, Hentgen Véronique, Courvoisier Natacha, Charlot-Lambrecht Isabelle, Damade Richard, Argenteuil Pizana Gabrielle, Fontanges Elisabeth, Morel Gautier, Roux Christian, Perard Laurent, Gaches Francis, Cacoub Patrice, Mekinian Arsène, Cohen Fleur, Margarit Nathalie, Salmon Jean-Hugues, Guillaume Séverine, Gilson Mélanie, Coutier Fabrice, Rouzaud Diane, Duhamel Alain, Combe Bernard, Jullien Denis, Gill Ghislaine, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Saint-Joseph [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPCité Médecine Paris Centre), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Necker - Enfants Malades [AP-HP], CH Belfort-Montbéliard, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Avicenne [AP-HP], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], CHU Rouen, Normandie Université (NU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut national de recherches archéologiques préventives (Inrap), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Cochin [AP-HP], PSA Peugeot Citroën (PSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital d'Instruction des Armées Laveran, Service de rhumatologie [Groupe Hospitalier Diaconesses Croix Saint Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation Ophtalmologique Adolphe de Rotschild, Service de Médecine Intensive et Réanimation [Tours], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Hôpital Foch [Suresnes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie (Hôpitaux Civils de Colmar), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Chimie Agro-Industrielle (CAI), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Trousseau [Tours], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Dax, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Hôpitaux Privés de Metz (HPMetz), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne [Centre hospitalier Lons le Saunier], Centre hospitalier Lons le Saunier, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], CHU Trousseau [APHP], CHU Amiens-Picardie, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Langues et civilisations à tradition orale (LACITO), Université Sorbonne Nouvelle - Paris 3-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS), Études Pharmaco-Immunologie (EPI), Université de La Réunion (UR), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, CHU Toulouse [Toulouse], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Club Rhumatismes et Inflammation, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), CHU Clermont-Ferrand, Université de Lille, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Centre Hospitalier Victor Jousselin de Dreux, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Belfort (Service de Rhumatologie), Oncology, Regional Hospital of Orleans, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Gabriel Montpied [Clermont-Ferrand], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, CHU Saint-Etienne, Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie [CHRU Montpellier], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Columbia University Irving Medical Center (CUIMC), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut du Mouvement et de l'appareil Locomoteur (IML), Service d'Anesthésie réanimation [CHU Tenon], Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Hopital Réné Dubos, Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine interne - hôpital européen Georges-Pompidou, Aix Marseille Université (AMU), Sorbonne Université (SU), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de La Réunion - Faculté de Lettres et Sciences humaines (UR FLSH), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe ENergie Electrique et SYStémique (LAPLACE-GENESYS), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cabinet Médical de Rhumatologie, Marseille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de dermatologie et allergologie [CHU Tenon], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Saint-André, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Joseph Ducuing, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Navier (NAVIER UMR 8205), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], communicable diseases, Disease, Logistic regression, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, Adrenal Cortex Hormones, Epidemiology, Immunology and Allergy, Medicine, 030212 general & internal medicine, 2. Zero hunger, education.field_of_study, glucocorticoids, Mortality rate, tumor necrosis factors, Intensive care unit, 3. Good health, Hospitalization, Autoinflammatory Disorders, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biological therapy, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hypertension, Female, Adult, medicine.medical_specialty, Immunology, Population, imported, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, Obesity, education, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, business, Body mass index
Abstract: ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).
Published: 2020

32. Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults

Author: Matthieu Mahevas, Julie Oniszczuk, Dil Sahali, Carole Hénique, Marie-Hélène Delfau-Larue, Mohamad Zaidan, Etienne Audureau, Vincent Frontera, Anissa Moktefi, Mario Ollero, Valérie Molinier-Frenkel, Khalil El Karoui, Alexandre Karras, Asma Beldi-Ferchiou, Vincent Audard, Imane Azzaoui, Evangeline Pillebout, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), service Anatomie et Cytologie Pathologique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Service de rhumatologie, CHU Bordeaux [Bordeaux], Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Nephrotic Syndrome, [SDV]Life Sciences [q-bio], Plasma Cells, 030232 urology & nephrology, Serum albumin, Gastroenterology, Glomerulonephritis, Membranous, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, B-Cell Activating Factor, Medicine, Humans, B-cell activating factor, Interleukin 6, ComputingMilieux_MISCELLANEOUS, Transplantation, Proteinuria, biology, business.industry, Nephrosis, Lipoid, Interleukin, Gamma globulin, Middle Aged, 3. Good health, 030104 developmental biology, Nephrology, Immunoglobulin M, Case-Control Studies, biology.protein, Female, medicine.symptom, business
Abstract: Background The recent success achieved with the use of B cell-depleting agents in some patients with minimal change nephrotic syndrome (MCNS) suggests an unexpected role for B lymphocytes in the pathogenesis of this immune-mediated glomerular disease. Nevertheless, no extensive B-cell phenotyping analysis has ever been performed in untreated adult patients soon after MCNS diagnosis. Methods We investigated the distribution of the different B-cell subpopulations in 22 untreated adult patients with biopsy-proven MCNS [MCNS relapse (MCNS-Rel)]. We compared these data with those for 24 healthy controls, 13 MCNS patients in remission (with no specific treatment) and 19 patients with idiopathic membranous nephropathy (IMN). Results Patients with MCNS-Rel or IMN had higher proteinuria and lower serum albumin and gammaglobulin levels (P Conclusions An increase in the proportion of circulating plasmablasts seems to be a hallmark of untreated MCNS in adult patients. Further studies are required to more precisely determine the phenotype and functions of these cells.
Published: 2020

33. Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy

Author: Lubka T. Roumenina, Philippe Chadebech, Gwellaouen Bodivit, Paula Vieira‐Martins, Anne Grunenwald, Idris Boudhabhay, Victoria Poillerat, Sadaf Pakdaman, Laurent Kiger, Alicia Jouard, Etienne Audureau, France Pirenne, Frédéric Galactéros, Véronique Frémeaux‐Bacchi, Pablo Bartolucci, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Henri Mondor, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Substitut du sang et pathologie moléculaire du globule rouge, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité des maladies génétiques du globule rouge, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Centre de référence des syndromes drépanocytaires majeurs-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Centre de référence des syndromes drépanocytaires majeurs-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and CHADEBECH, Philippe
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, medicine.medical_specialty, Adolescent, Cell Count, CD59, Anemia, Sickle Cell, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Hemolysis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Hydroxyurea, complement, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], heme, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Complement Activation, 030304 developmental biology, Whole blood, 0303 health sciences, Innate immune system, Chemistry, CD46, Sickle cell disease, Hemopexin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, sC5b-9, 3. Good health, Complement system, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Female, 030215 immunology
Abstract: International audience; The complement system is an innate immune defense cascade that can cause tissue damage when inappropriately activated. Evidence for complement over activation has been reported in small cohorts of patients with sickle cell disease (SCD). However, the mechanism governing complement activation in SCD has not been elucidated. Here, we observe that the plasma concentration of sC5b-9, a reliable marker for terminal complement activation, is increased at steady state in 61% of untreated SCD patients. We show that greater complement activation in vitro is promoted by SCD erythrocytes compared to normal ones, although no significant differences were observed in the regulatory proteins CD35, CD55, and CD59 in whole blood. Complement activation is positively correlated with the percentage of dense sickle cells (DRBCs). The expression levels of CD35, CD55, and CD59 are reduced in DRBCs, suggesting inefficient regulation when cell density increases. Moreover, the surface expression of the complement regulator CD46 on granulocytes was inversely correlated with the plasma sC5b-9. We also show increased complement deposition in cultured human endothelial cells incubated with SCD serum, which is diminished by the addition of the heme scavenger hemopexin. Treatment of SCD patients with hydroxyurea produces substantial reductions in complement activation, measured by sC5b-9 concentration and upregulation of CD46, as well as decreased complement activation on RBCs in vitro. In conclusion, complement over activation is a common pathogenic event in SCD that is associated with formation of DRBCs and hemolysis. And, it affects red cells, leukocytes and endothelial cells. This complement over activation is partly alleviated by hydroxyurea therapy.
Published: 2020

34. Molecular testing for respiratory pathogens in sickle cell disease adult patients presenting with febrile acute chest syndrome

Author: Giovanna Melica, Anoosha Habibi, Jean-Winoc Decousser, R. Lepeule, Keyvan Razazi, Etienne Audureau, Constance Guillaud, A. Raffetin, Slim Fourati, Pablo Bartolucci, S. Gallien, Mehdi Khellaf, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Adult, Male, medicine.medical_specialty, Pneumopathie aiguë communautaire, Fever, medicine.drug_class, Drépanocytose, [SDV]Life Sciences [q-bio], Antibiotics, Pneumonia, Viral, Disease, Anemia, Sickle Cell, medicine.disease_cause, Article, Serology, 03 medical and health sciences, Acute community-acquired pneumonia, Young Adult, Internal medicine, Acute Chest Syndrome, Pneumonia, Bacterial, Medicine, Humans, Respiratory system, 0303 health sciences, Bacteria, 030306 microbiology, business.industry, Sickle cell disease, Biologie moléculaire, medicine.disease, Acute chest syndrome, 3. Good health, Pneumonia, Infectious Diseases, Molecular Diagnostic Techniques, Viruses, Etiology, Female, Rhinovirus, business, Nucleic acid detection, Nucleic Acid Amplification Techniques
Abstract: Highlights • Less than 20% of febrile acute chest syndromes are microbiologically documented in adults presenting with sickle cell disease. • Molecular testing for respiratory pathogens slightly improves the microbiological diagnosis for viral detection but allows for reducing the antibiotic therapy duration. • Beyond the technical limits of microbiological molecular testing in standard clinical settings, our findings suggest the limited role of infections in the pathophysiology of acute chest syndrome., Background Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. Methods We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. Results A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P = 0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. Conclusion Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.
Published: 2020

35. Defining Blood Group Gene Reference Alleles by Long-Read Sequencing: Proof of Concept in the ACKR1 Gene Encoding the Duffy Antigens

Author: Yann, Fichou, Isabelle, Berlivet, Gaëlle, Richard, Christophe, Tournamille, Lilian, Castilho, Claude, Férec, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire d’Excellence GR-Ex, Paris, France, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Campinas/Hemocentro-Unicamp [Campinas, Brazil], CHRU Brest, F-29200 Brest, France, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, EFS, UMR 1078, GGB, Université de Brest, 29200 Brest, INSERM, and PODEUR, Sophie
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, ComputingMilieux_MISCELLANEOUS, Research Article
Abstract: BACKGROUND: In the novel era of blood group genomics, (re-)defining reference gene/allele sequences of blood group genes has become an important goal to achieve, both for diagnostic and research purposes. As novel potent sequencing technologies are available, we thought to investigate the variability encountered in the three most common alleles of ACKR1, the gene encoding the clinically relevant Duffy antigens, at the haplotype level by a long-read sequencing approach. MATERIALS AND METHODS: After long-range PCR amplification spanning the whole ACKR1 gene locus (∼2.5 kilobases), amplicons generated from 81 samples with known genotypes were sequenced in a single read by using the Pacific Biosciences (PacBio) single molecule, real-time (SMRT) sequencing technology. RESULTS: High-quality sequencing reads were obtained for the 162 alleles (accuracy >0.999). Twenty-two nucleotide variations reported in databases were identified, defining 19 haplotypes: four, eight, and seven haplotypes in 46 ACKR1*01, 63 ACKR1*02, and 53 ACKR1*02N.01 alleles, respectively. DISCUSSION: Overall, we have defined a subset of reference alleles by third-generation (long-read) sequencing. This technology, which provides a “longitudinal” overview of the loci of interest (several thousand base pairs) and is complementary to the second-generation (short-read) next-generation sequencing technology, is of critical interest for resolving novel, rare, and null alleles.
Published: 2020

36. Methylprednisolone-induced immune thrombocytopenia

Author: Raoul Herbrecht, Bénédicte Lebrun-Vignes, Marie Dubert, Marc Michel, Matthieu Mahévas, Jean-Pierre Marolleau, Jean-Baptiste Méric, Antoine Froissart, Philippe Bierling, Michel Ducreux, Emilie Le Toriellec, Laure Croisille, Laure Thomas, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Etablissement Français du Sang [Créteil], Centre régional de pharmacovigilance [CHU Henri-Mondor], CHU Henri Mondor, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Intercommunal de Créteil (CHIC), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Purpura, Thrombocytopenic, Idiopathic, business.industry, [SDV]Life Sciences [q-bio], Platelet Glycoprotein GPIIb-IIIa Complex, Hematology, Middle Aged, Methylprednisolone, Antibodies, Immune thrombocytopenia, Purpura, Immunology, medicine, Humans, Female, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, Aged, medicine.drug
Abstract: International audience
Published: 2020

37. Efficacy and Safety of a Combination of Thrombopoietin Receptor Agonist with an Immunosuppressant Therapy for the Management of Multirefractory Adult ITP: Results from a Retrospective, Multicenter, Observational Study

Author: Etienne Crickx, Bouchra Asli, Marc Ruivard, Matthieu Mahévas, Mikael Ebbo, Bertrand Godeau, Etienne Rivière, Louis Terriou, Sylvain Audia, Marc Michel, Jean Pierre Marolleau, Guillaume Moulis, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Edouard Herriot-Lyon, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), DESSAIVRE, Louise, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Thrombopoietin receptor, Agonist, medicine.medical_specialty, medicine.drug_class, business.industry, [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Biochemistry, [SDV] Life Sciences [q-bio], Internal medicine, medicine, Observational study, business, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction Multirefractory adult ITP, defined as no response to splenectomy, rituximab, and thrombopoietin receptor agonists (TPO-Ra), is associated with high morbidity and mortality. In a previous study, we have shown that combining an immunosuppressant therapy with one TPO-Ra could be a promising therapeutic strategy for managing patients with multirefractory ITP. Objective The aim of this study was to assess the efficacy and safety of such combination in multirefractory ITP on a larger series of patients. Patients and methods We conducted a retrospective, multicenter, observational study in France. Adult patients treated by a combination of a TPO-Ra with an immunosuppressant therapy (i.e., mycophenolate mofetil, azathioprine, ciclosporin, everolimus, or cyclophosphamide) for chronic (> 12 months) or persistent (> 3 months) multirefractory ITP, were included through the national reference center for adult immune cytopenia (CERECAI) network. Multirefractory ITP was defined as disease not responding to rituximab, to splenectomy (or contraindication to splenectomy), and to the 2 TPO-Ras licensed in France (romiplostim and eltrombopag) administered at the maximal approved dose. Clinical and biological data were retrospectively collected using a standardized form. Complete response (CR) was defined by a platelet count >100 x109/L and response (R) by a platelet count between 30-100 x109/L with at least a 2-fold increase from baseline, according to the international recommendations. Results Thirty-one patients (65% female, median age 57 years [range 23 - 82]) were included. Five (16%) of them had secondary ITP (Evans syndrome (n=2), systemic lupus (n=1) with antiphospholipid syndrome (APS), primary APS (n=1), and Waldenstrom macroglobulinemia (n=1). Four patients had a monoclonal gammopathy of undetermined significance, and 11 (35%) had antinuclear antibodies (titer >1/160) without definite clinical autoimmune disease. All patients had previously received corticosteroids and 16/31 (52%) were corticosteroid-refractory. Previous treatments lines also included intravenous immunoglobulin (28/31, 90%) and at least one immunosuppressant therapy (16/31, 52%). Splenectomy was performed in 25 patients (81%), and not performed in the remaining 6 patients because of advanced age and comorbidities (n=3), underlying APS (n=2), or patient refusal (n=1). At the time of treatment combination initiation, median ITP duration was 57 months [3 - 393], with 28/31 (90%) chronic ITP and 3/31 (10%) persistent ITP. Bleeding symptoms were present in 23 patients (74%) and the median platelet count was 10 x109/L [range 1 - 35]. The combination regiment included eltrombopag (n=18) or romiplostim (n=13), associated with either mycophenolate mofetil (n=15), azathioprine (n=12), cyclophosphamide (n=2), ciclosporine (n=1), or everolimus (n=1). Median duration of combination therapy was 12 months [range 1 - 103]. Nineteen patients (61%) had no therapeutic intervention other than the combined treatment, while 10 patients were also given corticosteroids (either short course of high dose steroids [n=5], or on a long-term at low dose [n=5]), and/or hydroxychloroquine (n=5). Overall, 81% of patients (25/31) achieved at least a R, including 19/31 (61%) CR. Among responders, the median time to response was 30 days [range 7 - 270], and the median duration of the response was 12 months [4 - 55]. Response rates were similar in patients who did not receive concomitant corticosteroids (59% CR, 12% R), and in patients that were previously exposed to immunosuppressant therapy given alone (63% CR, 25% R). Regarding safety, 13/31 (42%) patients experienced at least one adverse event potentially related to treatment, including 7 severe adverse events. Three patients without APS but who were splenectomized had a thromboembolic event, including 3 deep vein thrombosis/pulmonary embolism, and 1 cerebral venous thrombosis; Three patients had an infection (one cholecystitis, one herpes zoster, and one dental abscess). After a median follow-up of 18 months [6-103], one patient died (from a previously diagnosed adenocarcinoma). Conclusion In summary, these data show that most of the patients managed for multirefractory ITP may benefit from the combination of TPOra with an immunosuppressant therapy by achieving a durable response. The safety profile of this combination in this population seems acceptable. Disclosures Moulis: Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding; Amgen: Other: meeting attendance grant; Grifols: Research Funding. Michel:Bioverativ: Consultancy; Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:LFB: Honoraria; Amgen: Research Funding; Amgen: Honoraria; Novartis: Honoraria. Mahevas:GSK: Research Funding. OffLabel Disclosure: Some immunosuppressant drugs were given off-label for adult ITP.
Published: 2020

38. Short in-Frame Insertions/Deletions in the Coding Sequence of the α-Globin Gene. Consequences of the 3D Structure and Resulting Phenotypes: Hb Choisy as an Example

Author: Alexandre G de Brevern, Henri Wajcman, Serge Pissard, Michael C. Marden, Celine Latouche, Jean Riou, Service de Biochimie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de génétique [CHU Mondor], CHU Henri Mondor, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and de Brevern, Alexandre G.
Subjects: hemoglobin (Hb) variant, Hemoglobins, Abnormal, [SDV]Life Sciences [q-bio], Clinical Biochemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, 0302 clinical medicine, INDEL Mutation, alpha-Globins, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, insertion/deletion (ins/del), Insertion deletion, Coding region, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nucleotide, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Gene, Genetics (clinical), Sequence (medicine), chemistry.chemical_classification, Genetics, Base Sequence, molecular modeling, Biochemistry (medical), Nucleic acid sequence, Hematology, Phenotype, Protein Structure, Tertiary, [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, Hemoglobin, a-Globin, 030215 immunology
Abstract: International audience; A small group of hemoglobin (Hb) variants result from 'in-frame' deletion/insertion (del/ins). We describe a new variant of this group (Hb Choisy), found on the α1 gene, which is the exact counterpart of a previously published deletional variant, Hb J-Biskra [codons 51-58 (or codons 52-59) (-24 bp) (-TCTGCCCAGGTTAAGGGCCACGGC); HBA1: c.157_180del (or HBA2)]. In Hb J-Biskra, the sequence Ser-Ala-Gln-Val-Lys-Gly-His-Gly located from positions α52(E1) to α59(E8) is deleted, while in Hb Choisy the same sequence (Ser-Ala-Gln-Val-Lys-Gly-His-Gly) is inserted at position α52(E1). The variant carrying the insertion appears to be less damaging than the one with the deletion. A possible explanation could be that the additional sequence is located in the C to E interhelical region, and is less disturbing to the general structure of the globin chain. This insertion/deletion (ins/del) is likely favored by the repetition, at an interval of 16 nucleotides, of an eight nucleotide sequence. Comparison of variants of this group, found in the HbVar database, shows that structural modifications resulting from insertions are frequently less damaging than that caused by deletions.
Published: 2018

39. Controlling the growth of Escherichia coli by layer-by-layer encapsulation

Author: André Pawlak, Sabrina Belbekhouche, Ollero, Mario, IMRB - PGD/'Pathophysiology of Glomerular Diseases' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC)
Subjects: Alginates, Aerobic bacteria, [SDV]Life Sciences [q-bio], Context (language use), 02 engineering and technology, medicine.disease_cause, 01 natural sciences, Chitosan, chemistry.chemical_compound, Colloid and Surface Chemistry, [CHIM] Chemical Sciences, 0103 physical sciences, Escherichia coli, medicine, Zeta potential, Animals, Humans, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, Microbial Viability, 010304 chemical physics, biology, Layer by layer, Surfaces and Interfaces, General Medicine, 021001 nanoscience & nanotechnology, biology.organism_classification, Polyelectrolyte, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], chemistry, Biophysics, 0210 nano-technology, Bacteria, Biotechnology
Abstract: Escherichia coli is one of the most common commensal aerobic bacteria in the gut microbiota of humans (and other mammals). Nevertheless, if left free to proliferate, it can induce a large range of diseases from diarrhoea to extra-intestinal diseases. In recent years, this bacterium had become increasingly resistant to antibiotics. It is therefore essential to implement new approaches able to maintain both bacterial viability and to control their proliferation. In this context, we developed a process to encapsulate Escherichia coli in polymer shells. We took advantage of the fact that this bacterium has a negatively charged surface and modified it via a layer-by-layer process, i.e. with oppositely charged polyelectrolyte pairs (namely chitosan as the polycation and alginate or dextran sulfate as polyanion). We successfully demonstrate the controlled coating of the bacterial surface via zeta potential measurement, the viability of the encapsulated bacteria and a delay in growth due to the multilayer coating. This delay was dependent on the number of polyelectrolyte layers.
Published: 2021

40. Development of a Personalized 3D Carotid Model for Cerebral Vasculopathy Monitoring in Sickle Cell Disease

Author: Pablo Bartolucci, Valentin Amar, Frédéric Segonds, Seguin Marion, Philippe Connes, Jean-Frédéric Gerbeau, Irene E. Vignon-Clementel, Laurène Lenoir, Nguyen-Peyre Kim-Anh, Nuriye Akçay, Suzanne Verlhac, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire Conception de Produits et Innovation (LCPI), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Etablissement Français du Sang [Île-de-France Mondor], Service d'imagerie médicale, Centre de référence de la drépanocytose, CHIC et Hôpital Debré, Créteil, France, Centre de Référence des Syndromes Drépanocytaires Majeurs, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_specialty, beta-globin, brain, [SDV]Life Sciences [q-bio], Immunology, Cell, Blood viscosity, coculture techniques, Disease, Biochemistry, Magnetic resonance angiography, sickle cell anemia, Internal medicine, medicine.artery, Anterior cerebral artery, Medicine, cerebrovascular accident in children, Ejection fraction, medicine.diagnostic_test, business.industry, whole blood, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Hypoxia (medical), abnormal hemoglobins, medicine.disease, anemia, exchange transfusion, Sickle cell anemia, doppler ultrasound, medicine.anatomical_structure, cardiovascular system, Cardiology, vascular diseases, medicine.symptom, business
Abstract: Introduction Sickle cell disease (SCD) is the most prevalent and severe monogenic disorder due to a mutation in the b-globin gene, responsible for the production of an abnormal hemoglobin (HbS) which polymerizes under hypoxia. Cerebral vasculopathy (CV) generally appearing during childhood, is responsible for ischemic stroke, making SCD the first etiology of stroke in children and young adults. To date, several biological and hemodynamical determinants have been identified in CV development such as severe anemia and/or high intracranial vascular flow velocities (> 200 cm/s). Chronic blood exchange transfusion decreases the risk of stroke in children having a pathological Doppler. However some patients still have a progressive impairment despite conventional treatment highlighting the need for new therapeutic strategies and a better understanding of the physiopathology. Therefore, by developing a 3D carotid model reproducing exactly vascular parameters of a SCD patient, we aim to: (i) determine the mechanisms of CV development in SCD, (ii) find new therapeutic approaches and (iii) predict the risk of progression of CV. Materials and methods Three-dimensional reconstructions of the internal carotid, middle cerebral and anterior cerebral artery from SCD patients were generated from magnetic resonance angiograms (MIMICS & 3Matics software, Materialise). We performed 3D simulations of the Navier-Stokes equations in patient specific geometries, including the state-of-the-art techniques of Computational Hemodynamics (multiscale coupling, backflow stabilization - FeLiSCe software) and other factors - such as the increase of the ejection fraction or the drop of peripheral resistances). Blood viscosity was based on a SCD cohort. Hemodynamic properties such as flow velocities (TMMV) and wall shear stress (WSS) in different areas of modelled carotid were then computed according to flow variations. Modelled carotid was obtained by 3D printing according to computer design (CATIA software). The next steps will consist in 1/importing doppler parameters from patients in a programmable pump for flow assays with blood mimicking fluid to measure TMMV and WSS at different areas in carotid, 2/incorporating resting or activated platelets in BMF to evaluate impact of high WSS on platelets degranulation, 3/developing a flow co-culture of smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) on carotid wall. HUVECs and SMCs at different zones of the carotid undergoing high/low WSS and oscillatory flow will be analysed Preliminary results Our preliminary results suggest that the carotid inlet flow but not blood viscosity is responsible for the pathological intra cranial velocities (Figure 1A). At high carotid inlet flow, areas of high and low WSS appeared in children (Figure 1B), suggesting the existence of turbulent flow that could lead to arterial wall damages. Figure 2A shows a 3D printed carotid reproducing the exact SCD child's one. The material of artificial carotid is compatible with HUVECs culture (Figure 2B) and fluidic experiment at high inlet flow (Figure 2C). On Doppler ultrasonography, the velocities measured in different sections of carotid were comparable to patient's data and these velocities were modified according to variations of inlet flow values. Conclusions and perspectives By modification of input conditions, our 3D personalized model can predict high or low vascular velocities areas and will allow a better understanding of the pathophysiological processes involved at the interface between abnormal flow and cells on carotid wall. This innovative model could be a pertinent tool to evaluate individually effectiveness of new therapeutic strategies in SCD patients. Furthermore, this work may constitute a proof of concept that can be transposed to other diseases. Disclosures Verlhac: Addmedica, Paris: Other: Financial Support; Bluebird Bio: Consultancy. Bartolucci:AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.
Published: 2019

41. Stereotactic Lung Irradiation in Mice Promotes Long-Term Senescence and Lung Injury

Author: Annaïg Bertho, Valérie Buard, Morgane Dos Santos, Olivier Guipaud, Serge Adnot, Agnès François, Vincent Paget, Frédéric Soysouvanh, Michele Mondini, Jérémy Lavigne, Eric Deutsch, Mohamed Amine Benadjaoud, Fabien Milliat, Georges Tarlet, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), This work was support by the ROSIRIS program and Institut de Radioprotection et de Sûreté Nucléaire funding., Service de radiotherapie, and Institut Gustave Roussi (IGR)
Subjects: Senescence, Cancer Research, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Lung injury, 030218 nuclear medicine & medical imaging, Ionizing radiation, 03 medical and health sciences, Mice, 0302 clinical medicine, Fibrosis, medicine, Animals, Radiology, Nuclear Medicine and imaging, Irradiation, Lung cancer, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Radiation, Lung, business.industry, Endothelial Cells, Dose-Response Relationship, Radiation, Lung Injury, medicine.disease, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Toxicity, business, Tomography, X-Ray Computed
Abstract: International audience; Purpose: Lung cancer will be treated more frequently using stereotactic body radiation therapy, and preclinical research tomodel long-term toxicity of ablative doses of radiation is crucial. Stereotactic lung irradiation of a small volume can induceradiation pneumonitis and fibrosis in normal tissues.Methods and Materials: Senescence has been reported to contribute to lung fibrosis, and we investigated in vivo the effects ofablative doses of ionizing radiation on senescence-associated processes. The left lung of p16$^{INK4a}$ -LUC knock-in mice wasexposed to a single dose or fractionated radiation doses in a millimetric volume using a small animal radiation research platform.Results: Single or fractionated ablative radiation induces acute and very long-term p16$^{INK4a}$ activation in the irradiated lungtarget volume associated with lung injury. We observed a panel of heterogeneous senescent cells including pneumocytes, macrophages,and endothelial cells that accumulated around the radiation-induced lung focal lesion, suggesting that different senescentcell types may contribute to radiation injury.Conclusions: This work provides important information on the long-term effects of ablative radiation doses in the normal lungand strongly suggests that stress-induced senescence is involved in stereotactic body radiation therapyeinduced late fibrosis.
Published: 2019

42. Bortezomib and dexamethasone, an original approach for treating multi‐refractory warm autoimmune haemolytic anaemia

Author: Bertrand Godeau, N. Costedoat, Jehane Fadlallah, Lionel Galicier, Nicolas Limal, Claire Fieschi, Sylvain Audia, Matthieu Mahévas, Etienne Crickx, Marc Michel, Eric Oksenhendler, Marion Malphettes, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Gastroenterology, Dexamethasone, Bortezomib, 03 medical and health sciences, Hemoglobins, Young Adult, 0302 clinical medicine, Refractory, Internal medicine, Induction therapy, medicine, Humans, Adverse effect, Glucocorticoids, Complete response, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, business.industry, Hematology, Off-Label Use, Middle Aged, medicine.disease, 3. Good health, Peripheral neuropathy, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, Drug Therapy, Combination, Female, Anemia, Hemolytic, Autoimmune, business, 030215 immunology, medicine.drug
Abstract: We report the off-label use of bortezomib combined with dexamethasone in eight adults with severe and multi-refractory warm auto-immune haemolytic anaemia (wAIHA). After six cycles of induction therapy, 6 of the 8 patients achieved response (3 complete response, 3 response). Response was obtained after a median of 2 (1-4) cycles. After a median follow-up of 14 (6-36) months, six patients maintained a response (bortezomib/dexamethasone maintenance, n = 4); five patients experienced at least one moderate adverse event, including peripheral neuropathy (n = 2). These results suggest that bortezomib/dexamethasone combination is a promising approach with acceptable toxicity for treating severe refractory wAIHA in adults.
Published: 2019

43. Predisposing factors for anti-D immune response in D − patients with chronic liver disease transfused with D + platelet concentrates

Author: Burin Des Roziers, Nicolas, Chadebech, Philippe, Malard, Lucile, Vingert, Benoit, Gallon, Philippe, Samuel, Didier, Djoudi, Rachid, Fillet, Anne-Marie, Pirenne, France, Etablissement Français du Sang [Île-de-France Mondor], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and CHADEBECH, Philippe
Subjects: [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Abstract: International audience; Background: Recent reports have indicated that the risk of anti-D alloimmunization following D-incompatible platelet (PLT) transfusion is low in hematology and oncology patients. We investigated the rate of anti-D alloimmunization in RhD-negative (D- ) patients with chronic liver disease transfused with D+ platelet concentrates (PCs) and the factors involved, at a liver transplant (LT) center.Study design and methods: We reviewed the blood bank database from January 2003 to October 2016. D- patients who had received D+ PLT transfusions were eligible if they had undergone antibody screening at least 28 days after the first D+ PC transfusion, had no previous or concomitant exposure to D+ blood products, and had not received anti-D immunoglobulins.Results: Six of the 56 eligible patients (10.7%) had anti-D antibodies. All had received whole blood-derived PCs. Four of 20 patients (20%) untransplanted or transfused before LT and only two of 36 patients (5.6%) transfused during or after LT produced anti-D antibodies. These two patients were on maintenance immunosuppression based on low-dose steroids and tacrolimus. The factors identified as significantly associated with anti-D immune response were the presence of red blood cell immune alloantibodies before D+ PLT transfusion (p = 0.003), and D+ PLT transfusion outside the operative and postoperative (5 days) periods for LT (p = 0.023).Conclusion: D- patients with chronic liver disease transfused with D+ PLTs before LT are at high risk of developing anti-D antibodies. Preventive measures should be considered for these patients.
Published: 2019

44. FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

Author: Frank Giton, Charlotte M. François, Ghislaine Garrel, Celine J. Guigon, Victoria Cluzet, Florence Petit, Joëlle Cohen-Tannoudji, Marie M Devillers, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and ORANGE, Colette
Subjects: 0301 basic medicine, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], ACTIVATION, 0302 clinical medicine, Endocrinology, Ovarian Follicle, PREANTRAL FOLLICLES, Follicular phase, SERUM GONADOTROPIN CONCENTRATIONS, Aromatase, Estradiol, Gene Expression Regulation, Developmental, IMMATURE MOUSE, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Receptors, FSH, Female, Gonadotropin, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, endocrine system, medicine.drug_class, ANTI-MULLERIAN HORMONE, LUTEINIZING-HORMONE, 030209 endocrinology & metabolism, Ovary, Biology, Gonadotropic cell, 03 medical and health sciences, FEMALE RATS, Internal medicine, PITUITARY, medicine, POSTNATAL-DEVELOPMENT, Animals, Granulosa cell proliferation, Cell Proliferation, Granulosa Cells, urogenital system, Luteinizing Hormone, Antral follicle, FOLLICLE-STIMULATING-HORMONE, Mice, Inbred C57BL, 030104 developmental biology, biology.protein, Follicle Stimulating Hormone, Gonadotropins, Hormone
Abstract: Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature follicle-stimulating hormone (FSH)-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by elevated levels of both gonadotropins and E2. We previously demonstrated in mice that elevated FSH concentrations are necessary to induce E2 production by preantral/early antral follicles through the stimulation of aromatase expression without supporting their growth. However, whether this action of FSH could involve AMH is unknown. Here, we show that Amh mRNA and protein abundance and serum AMH levels are elevated in infantile mouse females, compared with those in adults. By experimentally manipulating FSH and E2 levels in infantile mice, we demonstrate that high FSH concentrations lower Amh expression specifically in preantral/early antral follicles, whereas E2 has no effect. Importantly, treatment of infantile ovaries in organotypic cultures with AMH decreases FSH-mediated expression of Cyp19a1 aromatase, but it does not alter the expression of cyclin D2-mediating granulosa cell proliferation. Overall, our data indicate that the infantile elevation in FSH levels suppresses Amh expression in preantral/early antral follicles, thereby favoring Cyp19a1 aromatase expression and E2 production. Together with recent discoveries that AMH can act on both the hypothalamus and the pituitary to increase gonadotropin levels, this work suggests that AMH is a critical regulator of the gonadotrope axis during the infantile period, thereby contributing to adult reproductive function programming.
Published: 2019

45. Cytokine changes in sickle-cell disease patients as markers predictive of the onset of delayed hemolytic transfusion reactions

Author: Philippe Chadebech, Marie-Amélie de Ménorval, Gwellaouen Bodivit, Alicia Jouard, Sadaf Pakdaman, Francoise Lelong, Anoosha Habibi, Frédéric Galactéros, Jean Claude Lecron, France Pirenne, CHADEBECH, Philippe, Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang Ile de France (EFS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Henry Mondor, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre de Référence des Syndromes Drépanocytaires Majeurs [AP-HP Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Institut Universitaire de Santé Publique [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_treatment, Immunology, Sickle-cell disease, Context (language use), Anemia, Sickle Cell, Disease, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Hemolysis, Biochemistry, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Humans, Immunology and Allergy, Macrophage, Blood Transfusion, Prospective Studies, Molecular Biology, business.industry, Transfusion, Transfusion Reaction, Interleukin, Hematology, medicine.disease, 3. Good health, 030104 developmental biology, Cytokine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cytokines, Female, DHTR, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Tumor necrosis factor alpha, business, Acute-phase patients
Abstract: International audience; Background: Changes in cytokine production are known to contribute to the pathogenesis of sickle-cell disease (SCD), particularly in painful acute complications (crises) and episodes of post-transfusion hemolysis. Little is known about cytokine profiles in patients with these complications.Study design and methods: We investigated possible associations between cytokine profile and the onset of delayed hemolytic transfusion reactions (DHTRs), particularly during acute-phase episodes, to improve characterization of the biological parameters predictive of such events. We included SCD patients with severe acute symptoms (n = 36) or steady-state disease (n = 31), both possibly leading to a DHTR (n = 18) event. Luminex® technology was used to determine the plasma concentrations of 23 cytokines.Results: Regardless of clinical context, the concentrations of interleukin (IL)-6, IL-10, inducible protein-10, and macrophage inflammatory protein-1β were higher in plasma samples from SCD patients than in those from healthy controls. IL-6 and IL-10 concentrations were even higher in acute-phase plasma samples from SCD patients. In addition, IL-27 and TNFα levels were higher, and IL-6 and RANTES levels were lower in acute-phase SCD patients just before the onset of DHTR than in patients experiencing painful occlusive episodes.Conclusion: In addition to reporting the plasma cytokine profiles of SCD patients in various clinical phases of the disease, we provide the first evidence of a significant association between low plasma TNFα concentration, high plasma IP-10 concentration and the onset of DHTR in SCD patients.
Published: 2020

46. Clinical severity in adult warm autoimmune hemolytic anemia and its relationship to antibody specificity

Author: Chadebech, Philippe, Loustau, Valentine, Janvier, Daniel, Languille, Laetitia, Ripa, Julie, Tamagne, Marie, Bierling, Philippe, Djoudi, Rachid, Godeau, Bertrand, Michel, Marc, Pirenne, France, Mahévas, Matthieu, Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de référence maladie rare des cytopénies auto-immunes de l'adulte (GECAI - Hôpital Henri-Mondor - UPEC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Etablissement Français du Sang [Ivry-sur-Seine] (E.F.S - Ile-de-France ), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CHADEBECH, Philippe
Subjects: Adult, Aged, 80 and over, Male, Erythrocyte Membrane, Age Factors, Disease Management, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Middle Aged, Autoantigens, Severity of Illness Index, Phagocytosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody Specificity, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Anemia, Hemolytic, Autoimmune, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Online Only Articles, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Biomarkers, Aged, Autoantibodies
Abstract: International audience; No abstract available
Published: 2018

47. Incidence and predictive score for delayed hemolytic transfusion reaction in adult patients with sickle cell disease

Author: Pablo Bartolucci, David Narbey, Bertrand Godeau, Jean-Daniel Lelièvre, Frédéric Galactéros, Rachid Djoudi, Mehdi Khellaf, Anoosha Habibi, Philippe Chadebech, Armand Mekontso-Dessap, Marc Michel, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Créteil], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHADEBECH, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Pediatrics, medicine.medical_specialty, Blood transfusion, Anemia, medicine.medical_treatment, Anemia, Sickle Cell, 030204 cardiovascular system & hematology, Hemolysis, Risk Assessment, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Blood Transfusion, Prospective Studies, Young adult, Prospective cohort study, business.industry, Incidence (epidemiology), Incidence, Transfusion Reaction, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Delayed hemolytic transfusion reaction, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Predictive value of tests, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Complication, business, 030215 immunology
Abstract: International audience; Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients.
Published: 2017

48. Rôle du chaperon moléculaire de l’alpha-hémoglobine dans la formation de l’hémoglobine et l’expression clinique de certaines hémoglobinopathies

Author: Véronique Baudin-Creuza, C Vasseur, BAUDIN-CREUZA, Véronique, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Ineffective erythropoiesis, Hémoglobine, Thalassémies, [SDV]Life Sciences [q-bio], Thalassemia, Clinical Biochemistry, medicine.disease_cause, Globules rouges, chemistry.chemical_compound, Biosynthesis, Marqueur érythroïde, medicine, Hemoglobin, chemistry.chemical_classification, Reactive oxygen species, AHSP chaperon de l’alpha-hémoglobine, biology, Chemistry, AHSP alpha-hemoglobin chaperone, Biochemistry (medical), Marker of erythroid precursors, Hematology, Thalassemias, medicine.disease, Molecular biology, 3. Good health, [SDV] Life Sciences [q-bio], Red blood cell, medicine.anatomical_structure, Chaperone (protein), biology.protein, Bone marrow
Abstract: International audience; Alpha-hemoglobin stabilizing protein (AHSP), described as a chaperone of alpha-hemoglobin (α-Hb), is synthesized at a high concentration in the erythroid precursors. AHSP specifically recognizes the G and H helices of α-Hb and forms a stable complex with free α-Hb until its association with the partner β-subunits. Unlike the free β-Hb which are soluble and form homologous tetramers, freshly synthesized α-Hb chains are highly unstable molecular species which precipitate and generate reactive oxygen species within the erythrocyte precursors of the bone marrow leading to apoptosis and ineffective erythropoiesis. AHSP protects the free α-Hb chains in maintaining it in the soluble state. In this review, we report data from the literature and our laboratory concerning the key role of AHSP in the biosynthesis of Hb and its possible involvement in some disorders of the red blood cell as well as the hemoglobinopathies and we discuss its use as a prognostic tool in thalassemia syndromes.
Published: 2015

49. Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination

Author: Moh-Klaren, Julia, Bodivit, Gwellaouen, Jugie, Myriam, Chadebech, Philippe, Chevret, Laurent, Mokhtari, Mostafa, Chamillard, Xavier, Gallon, Philippe, Tissières, Pierre, Bierling, Philippe, Djoudi, Rachid, Pirenne, France, Burin-des-Roziers, Nicolas, Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Réanimation Néonatale et Pédiatrique [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Endotoxines, Structures et Réponses de l'hôte (ESHR), Département Microbiologie (Dpt Microbio), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and CHADEBECH, Philippe
Subjects: [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV]Life Sciences [q-bio], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Background: Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma.Study design and methods: We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products.Results: The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP.Conclusion: Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants.
Published: 2017

50. Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

Author: Sylvie Chevret, Suzanne Verlhac, Elisabeth Ducros-Miralles, Jean-Hugues Dalle, Regis Peffault de Latour, Mariane de Montalembert, Malika Benkerrou, Corinne Pondarré, Isabelle Thuret, Corinne Guitton, Emmanuelle Lesprit, Maryse Etienne-Julan, Gisèle Elana, Jean-Pierre Vannier, Patrick Lutz, Bénédicte Neven, Claire Galambrun, Catherine Paillard, Camille Runel, Charlotte Jubert, Cécile Arnaud, Annie Kamdem, Valentine Brousse, Florence Missud, Marie Petras, Lydia Doumdo-Divialle, Claire Berger, Françoise Fréard, Olivier Taieb, Elise Drain, Monique Elmaleh, Manuela Vasile, Yacine Khelif, Myriam Bernaudin, Philippe Chadebech, France Pirenne, Gérard Socié, Françoise Bernaudin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Robert Debré, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université des Antilles (UA), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CHU de la Martinique [Fort de France], Hôpital Charles Nicolle [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital de Hautepierre [Strasbourg], Université de Strasbourg (UNISTRA), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Saint-Etienne, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Université de Caen Normandie (UNICAEN), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Radiologie [Créteil], CHI Créteil, Hôpital Robert Debré Paris, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pointe à Pitre], CHU Fort de France, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Normandie Université (NU)-Normandie Université (NU), Service d'immuno-hématologie pédiatrique [CHU Necker], Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Groupe hospitalier Pellegrin, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Rouen, CHADEBECH, Philippe, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Jean Monnet - Saint-Étienne (UJM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, Pediatrics, Ultrasonography, Doppler, Transcranial, medicine.medical_treatment, Hematopoietic stem cell transplantation, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cognition, 0302 clinical medicine, Genetic randomization, Medicine, Pharmacology (medical), Prospective Studies, Child, Prospective cohort study, Stroke, General Medicine, Sickle cell anemia, 3. Good health, Cerebral vasculopathy, Research Design, Child, Preschool, 030220 oncology & carcinogenesis, Female, medicine.medical_specialty, Iron Overload, Randomization, Adolescent, Anemia, Sickle Cell, Chronic transfusion, 03 medical and health sciences, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Blood Transfusion, Adverse effect, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Transfusion Reaction, Transcranial Doppler, medicine.disease, Surgery, Transplantation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: Background Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. Design DREPAGREFFE ( NCT01340404 ) is a multicenter, prospective trial enrolling SCA children younger than 15 years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥ 200 cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1 year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. Objectives To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. Discussion DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.
Published: 2017

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