Author: "Fédération Hospitalo-Universitaire OMICARE" / Publication Year Range: Last 50 years - Searchworks@Jio Institute Digital Library Search Results

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183 results on '"Fédération Hospitalo-Universitaire OMICARE"'

1. A Homozygous Missense Variant in PPP1R1B/DARPP‐32 Is Associated With Generalized Complex Dystonia

Author: Anne Molitor, Gaoqun Zhang, Bruno Rinaldi, Sepand Rastegar, Muhammad Umair, Seiamak Bahram, Sylvie Friant, Mathieu Anheim, Sylvain Mayeur, Benoit Lhermitte, Stefan T. Arold, Amjad Khan, Béatrice Lannes, Raphael Carapito, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), CHU Strasbourg, Karlsruher Institut für Technologie (KIT), Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), King Saud Bin Abdulaziz University for Health Sciences [Riyadh] (KSAU-HS), Centurion University of Technology and Management [India], King Abdullah University of Science and Technology (KAUST), Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), univOAK, Archive ouverte, Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Dopamine and cAMP-Regulated Phosphoprotein 32, autosomal recessive generalized dystonia, Movement disorders, Substantia nigra, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, 0302 clinical medicine, medicine, Missense mutation, Animals, Humans, Generalized epilepsy, Zebrafish, Exome sequencing, PPP1R1B, 030304 developmental biology, Dystonia, Genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Homozygote, medicine.disease, biology.organism_classification, 3. Good health, DARPP-32, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Dystonic Disorders, Neurology (clinical), medicine.symptom, exome sequencing, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: The dystonias are a heterogeneous group of hyperkinetic disorders characterized by sustained or intermittent muscle contractions that cause abnormal movements and/or postures. Although more than 200 causal genes are known, many cases of primary dystonia have no clear genetic cause.Objectives: To identify the causal gene in a consanguineous family with three siblings affected by a complex persistent generalized dystonia, generalized epilepsy, and mild intellectual disability.Methods: We performed exome sequencing in the parents and two affected siblings and characterized the expression of the identified gene by immunohistochemistry in control human and zebrafish brains.Results: We identified a novel missense variant (c.142G>A (NM_032192); p.Glu48Lys) in the protein phosphatase 1 regulatory inhibitor subunit 1B gene (PPP1R1B) that was homozygous in all three siblings and heterozygous in the parents. This gene is also known as dopamine and cAMP-regulated neuronal phosphoprotein 32 (DARPP-32) and has been involved in the pathophysiology of abnormal movements. The uncovered variant is absent in public databases and modifies the conserved glutamate 48 localized close to the serine 45 phosphorylation site. The PPP1R1B protein was shown to be expressed in cells and regions involved in movement control, including projection neurons of the caudate-putamen, substantia nigra neuropil, and cerebellar Purkinje cells. The latter cells were also confirmed to be positive for PPP1R1B expression in the zebrafish brain.Conclusions: We report the association of a PPP1R1B/DARPP-32 variant with generalized dystonia in man. It might be relevant to include the sequencing of this new gene in the diagnosis of patients with otherwise unexplained movement disorders. © 2021 International Parkinson and Movement Disorder Society.
Published: 2022
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2. Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort

Author: Qian Zhang, Paul Bastard, Haiguo Wu, Adrian Gervais, Seiamak Bahram, Sylvain Mayeur, Sharvari Gujja, Anne Thomas, Alexandre Lederle, Julie Helms, Christiane Moog, Xavier Mariette, Alain Viari, Tristan Stemmelen, Christine Carapito, Olivier Hermine, Richard Li, Daniel A. Lidar, Cécile Macquin, Jean Sibilia, Géraldine Laumond, Shweta Kailasan, Leslie Muller, Sabrina Bibi-Triki, Sylvie Schmidt, Aurélie Hirschler, Raony Guimaraes, Michael Simons, Anne Molitor, Francis Schneider, Damien Sanlaville, Thiên-Nga Chamaraux-Tran, Samira Fafi-Kremer, Pierre-Louis Tharaux, Thomas Chittenden, Angélique Pichot, A. Hanauer, Raphael Carapito, Mirjana Radosavljevic, Véronique Rolli, Bernard Goichot, Yvon Ruch, Olivier Collange, Ouria Tahar, Julien Pottecher, Khaldoun Kuteifan, Razieh Mohseninia, Perrine Spinnhirny, Alice Bernard, Bernard Drenou, Jean-Laurent Casanova, Elisa Pin, Jeffrey R. Gulcher, Paul-Michel Mertes, M. Javad Aman, Peter Nilsson, Jose Malagon-Lopez, François Danion, Yves Hansmann, Ferhat Meziani, Maleka Schenck, Nicodème Paul, Annabel Larnicol, Julia Frappier, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Genuity Science [Boston], Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Yale School of Medicine [New Haven, Connecticut] (YSM), Hôpital Bicêtre, 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, 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), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Integrated biotherapeutics [Rockville], Royal Institute of Technology [Stockholm] (KTH ), Auragen [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [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)-Centre Léon Bérard [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), 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), Harvard Medical School [Boston] (HMS), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), CARAPITO, Christine, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Yale University School of Medicine, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), 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), 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 de Paris (UP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and 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)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Aucun, MEDLINE, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Medicine, Humans, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, Confounding, COVID-19, Membrane Proteins, General Medicine, Respiration, Artificial, 3. Good health, ADAM Proteins, Intensive Care Units, 030220 oncology & carcinogenesis, Cohort, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Identification (biology), business
Abstract: International audience; The etiopathogenesis of critical COVID-19 remains unknown. Indeed given major confounding factors (age and comorbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major comorbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 “critical” (in the ICU under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from non-critical patients, several driver genes promoted critical COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was supported in a second independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible.
Published: 2021
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3. Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series

Author: Frank Verhoeven, Renaud Felten, Daniel Wendling, Martin Soubrier, Alain Saraux, Eric Toussirot, Jean Sibilia, Charles Dervout, V. Grobost, Bruno Gombert, Divi Cornec, Hervé Lobbes, Marc Ruivard, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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]), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Equipe Plate-forme GENOMAX (Inserm U1109), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Besançon, Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CCSD, Accord Elsevier, 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), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Lymphocyte B et Auto-immunité (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, Cyclophosphamide, [SDV.IMM] Life Sciences [q-bio]/Immunology, Large granular lymphocytic leukemia, Population, Gastroenterology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Cyclosporin a, medicine, Humans, Rheumatoid factor, 030212 general & internal medicine, education, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Middle Aged, medicine.disease, 3. Good health, Leukemia, Large Granular Lymphocytic, Methotrexate, Anesthesiology and Pain Medicine, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, business, medicine.drug
Abstract: Objectives To assess the efficacy and tolerance profile of rituximab in rheumatoid arthritis (RA)-associated large granular lymphocyte leukemia (LGLL). Methods Multicenter retrospective case series. Inclusion criteria were RA defined by the ACR/EULAR 2010 criteria and LGLL defined by absolute LGL count ≥ 0.3 × 109/L with evidence of an expanded clonal LGL population (flow cytometry, TCR-γ polymerase chain reaction, or Stat3 mutation). Results Fourteen patients (10 women, mean age 55.2 ± 14.2 years) included; 13 were seropositive for anti-cyclic citrullinated peptides (n = 11) or rheumatoid factor (n = 10). LGLL diagnosis was made 9.5 [IQR: 3.25;15.5] years after RA diagnosis. Thirteen patients had T-LGLL. Rituximab was the first-line therapy for LGLL for 4 patients. Previous treatment lines included methotrexate (n = 7), cyclophosphamide (n = 2), cyclosporin A (n = 1), or granulocyte colony-stimulating factor (n = 4). Rituximab was used in monotherapy (n = 8) or associated to methotrexate (n = 3), granulocyte colony-stimulating factor (n = 2), or alkylating agents (n = 1). The number of rituximab cycles ranged from 1 to 11 (median 6), with high heterogeneity in dosing regimens. Median duration response after rituximab initiation was 35 [IQR: 23.5;41] months. The overall response rate was 100%: 8 patients experienced complete response (normalization of blood count and LGL ≤ 0.3 × 109/L) and 6 experienced partial responses (improvement in blood counts without complete normalization). The tolerance profile was good, with no infectious complications. Conclusion rituximab appears as a valuable therapeutic option for RA-associated LGLL.
Published: 2020
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4. Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice

Author: Amira Sayeh, Gaëlle Aubertin-Kirch, Catherine Isabelle Gros, Laetitia Higel, Michel Fischbach, Jean-Philippe Dillenseger, Claus Peter Schmitt, André Constantinesco, Philippe Choquet, Fabien Bornert, Ariane Zaloszyc, Christian Goetz, Siamak Bahram, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Hautepierre [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Heidelberg University, Imagerie Préclinique-UF6237, Pôle d'imagerie [Strasbourg], Nanomédecine Régénérative (NanoRegMed), Medical Image Analysis Center (MIAC AG), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University of Freiburg [Freiburg], GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg] (FJ-HLA), Laboratoire International Associé (LIA), Nouvel Hôpital Civil de Strasbourg, and univOAK, Archive ouverte
Subjects: Radiology and Medical Imaging, [PHYS.PHYS]Physics [physics]/Physics [physics], Anabolism, Radionuclide imaging, business.industry, General Neuroscience, Subcutaneous application, Planar scintigraphy, Growth, General Medicine, Physique [physics]/Physique [physics], Biochemistry, General Biochemistry, Genetics and Molecular Biology, Mice, Orthopedics, Medicine, [PHYS.PHYS] Physics [physics]/Physics [physics], Nuclear medicine, business, General Agricultural and Biological Sciences, Developmental Biology
Abstract: Background To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. Methods Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. Results A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. Conclusion This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.
Published: 2021
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5. NLRP3- and AIM2-autonomy in a mouse model of MSU crystal-induced acute inflammation in vivo highlights imiquimod-dependent targeting of Il-1E expression as relevant therapy for gout patients

Author: Mariotte, Alexandre, De Cauwer, Aurore, Po, Chrystelle, Abou-Fayçal, Cherine, Pichot, Angélique, Paul, Nicodème, Aouadi, Ismael, Carapito, Raphael, Frisch, Benoit, Macquin, Cécile, Chatelus, Emmanuel, Sibilia, Jean, Armspach, Jean-Paul, Bahram, Seiamak, Georgel, Philippe, Frisch, Benoit, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Equipe 2 - Bases Moléculaires de la Progression des Cancers du Poumon, Inserm U823, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Plate-forme GENOMAX (Inserm U1109), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, Rhumatologie, CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ICube Laboratory, University of Strasbourg, CNRS, France, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: L'article est publié dans la revue sous le titre définitif :"A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients"; International audience; The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1 in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1 secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. Here, we provide an extensive clinical, biological and molecular characterization of the acute uratic inflammation mouse model induced by subcutaneous injection of MSU crystals, which accurately mimics human gout. Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities, among which the use of topical application of imiquimod to promote interferon-dependent anti-inflammatory action maybe relevant. All rights reserved. No reuse allowed without permission. (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
Published: 2020

6. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus host disease in conjunction with the CMV status

Author: Philippe Moreau, Machteld Oudshoorn, Catherine Paillard, Valérie Dubois, Raphael Carapito, Irina Kotova, Antoine Toubert, Ismail Aouadi, Perrine Spinnhirny, Eric Spierings, A. Parissiadis, Ibrahim Yakoub-Agha, Mauricette Michallet, Myriam Labalette, Seiamak Bahram, Régis Peffault de Latour, Jürgen Kuball, Mohamad Mohty, Christophe Picard, Bronno van der Holt, Didier Blaise, Ryad Tamouza, Myriam Maumy-Bertrand, Frédéric Bertrand, Pascale Loiseau, Véronique Rolli, Jan J. Cornelissen, Aurore Morlon, Anne Cesbron, Gérard Socié, Yasuo Morishima, Peter A. von dem Borne, Frans H.J. Claas, Cécile Macquin, Angélique Pichot, Bruno Lioure, Dominique Charron, Katia Gagne, Equipe Plate-forme GENOMAX (Inserm U1109), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg] (FJ-HLA), Laboratoire International Associé (LIA), INSERM Franco-Japanese Nextgen HLA Laboratory[Nagano], Pôle de Biologie - Laboratoire d’Immunologie [Nouvel Hôpital Civil, Strasbourg] (Plateau Technique de Biologie), Nouvel Hôpital Civil - NHC [Strasbourg], BIOMICA SA [Strasbourg], Etablissement Français du Sang [Nantes], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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), 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), Europdonor operated by Matchis Foundation [Leiden], Leiden University Medical Center (LUMC), Erasmus MC Cancer Institute, Rotterdam, Laboratoire d'Immunologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Medical Center [Utrecht], Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), 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), Hôpital Hôtel-Dieu [Paris], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre & marie Curie, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Aichi Cancer Center Research Institute, This work was supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), and the INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), all to SB, from the University of Strasbourg (IDEX UNISTRA) to CP and SB, from the European regional development fund (European Union) INTERREG V program (project n°3.2 TRIDIAG) to RC and SB, and from MSD-Avenir grant AUTOGEN to SB., We would like to thank Prof. Robert Zeiser (University of Freiburg/Germany) for critical reading of this manuscript. We thank Martin Verniquet for critical review of statistical analyses. We would also like to thank Nicole Raus (SFGM-TC, Lyon, France) for retrieving the clinical data from the ProMISe database., Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), 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), Universiteit Leiden, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Hematology, Erasmus MC other, and Bernardo, Elizabeth
Subjects: medicine.medical_specialty, Congenital cytomegalovirus infection, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Typing, Amino Acids, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Graft-versus-host disease, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, business, 030215 immunology
Abstract: International audience; Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1 and MICA loci. HLA-DP typing was further available. MICB98 mismatches were significantly associated with an increased incidence of acute (grade II-IV: HR, 1.20; 95% CI, 1.15 to 1.24; P < 0.001; grade III-IV: HR, 2.28; 95% CI, 1.56 to 3.34; P < 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P < 0.001). MICB98 matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98 mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P < 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.
Published: 2020
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7. Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond–like features

Author: Carapito, Raphael, Konantz, Martina, Paillard, Catherine, Miao, Zhichao, Pichot, Angélique, Leduc, Magalie, Yang, Yaping, Bergstrom, Katie, Mahoney, Donald, Shardy, Deborah, Alsaleh, Ghada, Naegely, Lydie, Kolmer, Aline, Paul, Nicodème, Hanauer, Antoine, Rolli, Véronique, Müller, Joëlle, Alghisi, Elisa, Sauteur, Loïc, Macquin, Cécile, Morlon, Aurore, Sancho, Consuelo Sebastia, Amati-Bonneau, Patrizia, Procaccio, Vincent, Mosca-Boidron, Anne-Laure, Marle, Nathalie, Osmani, Nael, Lefebvre, Olivier, Goetz, Jacky, Unal, Sule, Akarsu, Nurten, Radosavljevic, Mirjana, Chenard, Marie-Pierre, Rialland, Fanny, Grain, Audrey, Béné, Marie-Christine, Eveillard, Marion, Vincent, Vincent, Guy, Julien, Faivre, Laurence, Thauvin-Robinet, Christel, Thevenon, Julien, Myers, Kasiani, Fleming, Mark, Shimamura, Akiko, Bottollier-Lemallaz, Elodie, Westhof, Eric, Lengerke, Claudia, Isidor, Bertrand, Bahram, Seiamak, Biotechnologie des interactions macromoléculaires (BIM), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Equipe Plate-forme GENOMAX (Inserm U1109), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Baylor College of Medicine (BCM), Baylor University, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Functional Genomics and Cancer, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire scribens, École Polytechnique de Montréal (EPM), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Cryopic, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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), Service d'hématologie biologique [Nantes] (Cytologie Hématologique), Hôtel-Dieu de Nantes-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie biologique [CHU de Dijon], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Çocuk Sağlığı ve Hastalıkları, Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), 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), 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), Service d'hématologie biologique (CHU de Dijon), Structure des macromolécules biologiques et mécanismes de reconnaissance (SMBMR), Centre National de la Recherche Scientifique (CNRS), Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiology of Human αβ and γδ T cells and Immunotherapeutic Applications (CRCINA - Département INCIT - Equipe 1), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-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 de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-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 de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Male, Models, Molecular, Neutropenia, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Research & Experimental Medicine, Protein Domains, Animals, Congenital Bone Marrow Failure Syndromes, Humans, Lipomatosis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Child, Bone Marrow Diseases, Genetic Association Studies, Zebrafish, ComputingMilieux_MISCELLANEOUS, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pancreas, Exocrine, Shwachman-Diamond Syndrome, Phenotype, Exocrine Pancreatic Insufficiency, Female, Signal Recognition Particle, Research Article
Abstract: Shwachman-Diamond syndrome (SDS) (OMIM # 260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. Using trio whole-exome sequencing (WES) in an SBDS-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in SRP54 (encoding signal recognition particle 54 kDa). These 3 patients shared congenital neutropenia linked with various other SDS phenotypes. 3D protein modeling revealed that the 3 variants affect highly conserved amino acids within the GTPase domain of the protein that are critical for GTP and receptor binding. Indeed, we observed that the GTPase activity of the mutated proteins was impaired. The level of SRP54 mRNA in the bone marrow was 3.6-fold lower in patients with SRP54-mutations than in healthy controls. Profound reductions in neutrophil counts and chemotaxis as well as a diminished exocrine pancreas size in a SRP54-knockdown zebrafish model faithfully recapitulated the human phenotype. In conclusion, autosomal dominant mutations in SRP54, a key member of the cotranslation protein-targeting pathway, lead to syndromic neutropenia with a Shwachman-Diamond-like phenotype.
Published: 2017
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8. Identification of early-induced broadly neutralizing activities against transmitted founder HIV strains

Author: Julie Lucas, Li-Yun Lin, Nicodème Paul, Géraldine Laumond, Jéromine Klingler, Sylvie Schmidt, Julia Frappier, Asma Essat, Laurence Meyer, Alicia Castro Gordon, C.é.cile Goujard, Seiamak Bahram, Christiane Moog, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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, Hôpital Bicêtre, Nouvel Hôpital Civil de Strasbourg, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 3.2 TRIDIAG, European Commission, EC, Agence Nationale de la Recherche, ANR, Institut National de la Santé et de la Recherche Médicale, Inserm, Institut Universitaire de France, IUF, European Regional Development Fund, ERDF, We thank all participants of the ANRS PRIMO cohort. This work was granted by the ANRS (Agence Nationale de Recherches sur le SIDA et les hépatites virales), the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020). Work in S.B.'s laboratory is supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), the INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), all the University of Strasbourg (IDEX UNISTRA), the European regional development fund (European Union) INTERREG V program (project no. 3.2 TRIDIAG) and MSD-Avenir grant AUTOGEN. The funders had no role in study design, data collection and interpretation or the decision to submit the work for publication., and European Project: 681032,H2020,H2020-PHC-2015-single-stage_RTD,EHVA(2016)
Subjects: transmitted/founders, Infectious Diseases, vaccine, Immunology, HIV, Humans, Immunology and Allergy, neutralizing antibodies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HIV Infections, acute infection, Broadly Neutralizing Antibodies
Abstract: International audience; Objectives:Broadly neutralizing antibodies have been proposed as key actors for HIV vaccine development. However, they display features of highly matured antibodies, hampering their induction by vaccination. As protective broadly neutralizing antibodies should be induced rapidly after vaccination and should neutralize the early-transmitted founder (T/F) viruses, we searched whether such antibodies may be induced following HIV infection.Design:Sera were collected during acute infection (Day 0) and at viral set point (Month 6/12) and the neutralizing activity against T/F strains was investigated. Neutralizing activity in sera collected from chronic progressor was analyzed in parallel.Methods:We compared neutralizing activity against T/F strains with neutralizing activity against non-T/F strains using the conventional TZM-bL neutralizing assay.Results:We found neutralizing antibodies (nAbs) preferentially directed against T/F viruses in sera collected shortly after infection. This humoral response evolved by shifting to nAbs directed against non-T/F strains.Conclusion:Although features associated with nAbs directed against T/F viruses need further investigations, these early-induced nAbs may display lesser maturation characteristics; therefore, this might increase their interest for future vaccine designs.
Published: 2022
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9. Quantitative description of <scp>SARS‐CoV</scp> ‐2 <scp>RT‐PCR</scp> , a cohort of 76 <scp>COVID</scp> ‐19 older hospitalized adults

Author: Anita Meyer, Patrick Karcher, Louise F. Porter, Erik Sauleau, Antonin Michaud, Samira Fafi-Kremer, Thomas Vogel, Georges Kaltenbach, Maxence Meyer, Amandine Leitner, Saïd Chayer, Aurélie Velay, Manon Leitner, Alexandre Boussuge, Marion Muller, Frédéric Blanc, Florentin Constancias, Lidia Calabrese, Elise Schmitt, Les Hôpitaux Universitaires de Strasbourg (HUS), Ortenau Klinikum Offenburg-Kehl [Offenburg, Germany], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), and univOAK, Archive ouverte
Subjects: Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID‐19‐Related Content, Humans, Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Statistics & numerical data, Letters to the Editor, Letter to the Editor, Aged, 80 and over, SARS-CoV-2, business.industry, Research, COVID-19, Virology, Hospitalization, Real-time polymerase chain reaction, COVID-19 Nucleic Acid Testing, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, France, Geriatrics and Gerontology, business
Abstract: PMCID: PMC8250917; No abstract available
Published: 2021
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10. Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases

Author: Sruthi Vijaya Retnakumar, Ramasatyaveni Geesala, Alexis Bretin, Julien Tourneur-Marsille, Eric Ogier-Denis, Thorsten Maretzky, Hang Thi Thu Nguyen, Sylviane Muller, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut du Médicament de Strasbourg (IMS [Strasbourg]), Carver College of Medicine [Iowa City], University of Iowa [Iowa City], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), 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), 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), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], CNRS, Région Grand-Est, INRAE, American Cancer Society [ACS-IRG-15-176-41], [ACS-IRG-18-165-43], Carver College of Medicine, University of Iowa Research Start-Up funds, University of Strasbourg Institute for Advanced Study (USIAS), Club francophone de l'autophagie (CFATG), European Regional Development Fund of the European Union, ImmuPharma-France, Ministere de la Recherche et de la Technologie, INSERM, ANR-10-LABX-0034,Medalis,Medalis Drug Discovery Center(2010), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), and European Project: CA15138,COST
Subjects: Peptide-based treatment, Immunology, Dextran Sulfate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammatory bowel diseases, Murine models, Colitis, Disease Models, Animal, Mice, Autophagy, Immunology and Allergy, Animals, [SDV.IMM]Life Sciences [q-bio]/Immunology, Carrier Proteins, Lysosomes
Abstract: International audience; Inflammatory bowel disease (IBD) is a serious public health problem in Western society with a continuing increase in incidence worldwide. Safe, targeted medicines for IBD are not yet available. Autophagy, a vital process implicated in normal cell homeostasis, provides a potential point of entry for the treatment of IBDs, as several autophagy-related genes are associated with IBD risk. We conducted a series of experiments in three distinct mouse models of colitis to test the effectiveness of therapeutic P140, a phosphopeptide that corrects autophagy dysfunctions in other autoimmune and inflammatory diseases. Colitis was experimentally induced in mice by administering dextran sodium sulfate and 2,4,6 trinitrobenzene sulfonic acid. Transgenic mice lacking both il-10 and iRhom2 - involved in tumor necrosis factor α secretion - were also used. In the three models investigated, P140 treatment attenuated the clinical and histological severity of colitis. Post-treatment, altered expression of several macroautophagy and chaperone-mediated autophagy markers, and of pro-inflammatory mediators was corrected. Our results demonstrate that therapeutic intervention with an autophagy modulator improves colitis in animal models. These findings highlight the potential of therapeutic peptide P140 for use in the treatment of IBD.
Published: 2022
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11. Coronavirus Disease 2019-Associated Mucormycosis in France: A Rare but Deadly Complication

Author: Danion, François, Letscher-Bru, Valérie, Guitard, Juliette, Sitbon, Karine, Dellière, Sarah, Angoulvant, Adela, Desoubeaux, Guillaume, Botterel, Francoise, Bellanger, Anne-Pauline, Gargala, Gilles, Uhel, Fabrice, Bougnoux, Marie-Elisabeth, Gerber, Victor, Michel, Justin, Cornu, Marjorie, Bretagne, Stéphane, Lanternier, Fanny, Merdji, Hamid, Delabranche, Xavier, Parrot, Antoine, Voiriot, Guillaume, Urbina, Tomas, Mebazaa, Alexandre, Chousterman, Benjamin, el Kalioubie, Ahmed, Six, Sophie, Coulon, Pauline, Sendid, Boualem, Anguel, Nadia, Damoisel, Charles, Mussini, Charlotte, Villate, Alban, Navellou, Jean-Christophe, Girault, Christophe, Cassagne, Carole, Augereau, Olivier, Dromer, Francoise, Garcia-Hermoso, Dea, Lortholary, Olivier, Alanio, Alexandre, Center of Experimental and Molecular Medicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], CHU Strasbourg, Dynamique des interactions hôte pathogène (DIHP), Mucoviscidose: physiopathologie et phénogénomique [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COVID-Mucor study group, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de parasitologie, mycologie, médecine tropicale [CHRU Tours], 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), CHU Henri Mondor [Créteil], Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Biologie Médicale de Référence Pneumopathie d'hypersensibilité, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Necker - Enfants Malades [AP-HP], Aix Marseille Université (AMU), CHU Lille, Service de Médecine Intensive et Réanimation [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Tenon [AP-HP], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), COVID-Mucor St Group Hamid Merdji (Médecine Intensive et Réanimation, Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Xavier Delabranche (Réanimation Chirugicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Antoine Parrot (Service de Pneumologie, Hôpital Tenon, AP-HP, Paris, France), Guillaume Voiriot (Service de Médecine Intensive et Réanimation, Hôpital Tenon, AP-HP, Paris, France), Tomas Urbina (Service de Réanimation Médicale, Hôpital Saint Antoine, AP-HP, Paris, France), Alexandre Mebazaa (Réanimation Chirurgicale, Hôpital Saint-Louis, AP-HP, Paris, France), Benjamin Chousterman (Réanimation, Hôpital Lariboisière, AP-HP, Paris, France), Ahmed El Kalioubie (Réanimation, CHU de Lille), Sophie Six (Réanimation, CHU de Lille, Lille, France), Pauline Coulon and Boualem Sendid (Service de Mycologie, CHU de Lille, France), Nadia Anguel (Réanimation Médicale, Le Kremlin-Bicêtre, AP-HP, Paris, France), Charles Damoisel (Réanimation Polyvalente, Clamart, AP-HP, France), Charlotte Mussini (Service d’Anatomopathologie, Le Kremlin-Bicêtre, AP-HP, Paris, France), Alban Villate (Hématologie, Tours, France), Jean-Christophe Navellou (Réanimation, CHU Besançon, France), Christophe Girault (Médecine Intensive et Réanimation, CHU Rouen, France), Carole Cassagne (Laboratoire de Mycologie, CHU Timone, Marseille, France), Olivier Augereau (Laboratoire de Microbiologie, Colmar, France), Francoise Dromer, Dea Garcia-Hermoso, Olivier Lortholary, Alexandre Alanio (CNRMA, Institut Pasteur, Paris, France)., Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)
Subjects: medicine.medical_specialty, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, CAM, Coronavirus disease 2019 (COVID-19), business.industry, Brief Report, General surgery, Mucormycosis, COVID-19, CAPA, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, mucormycosis, AcademicSubjects/MED00290, Infectious Diseases, Oncology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, business, Complication
Abstract: We studied COVID-19 associated mucormycosis based on 17 cases reported nationwide and assessed the differences with India. They differed by frequencies of diabetes mellitus (47% in France versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites (12% versus >80% rhino-orbito-cerebral) and prognosis (88% mortality versus, We reported 17 cases of COVID-19 associated mucormycosis in France. Compared to India, they differed by frequencies of diabetes mellitus (47% versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites and mortality (88% versus
Published: 2022
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12. Complex Allele with Additive Gain-of-Function STING1 Variants in a Patient with Cavitating Lung Lesions and Aspergillosis

Author: Aurélien, Guffroy, Yannick, Dieudonné, Vincent, Gies, François, Danion, Yves, Hansmann, Couvet, Sandrine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Centre National de Référence des Maladies Auto-immunes et Systémiques Rares Est Sud Ouest (CNR RESO), and and Study group: Anne-Sophie Korganow, Julien Tarabeux, Yvon Ruch, Pauline Soulas-Sprauel, Stéphane Giorgiutti, Nadège Wadier, Bénédicte Gérard, Elsa Nourisson, Nadia Nathan, Marie Legendre, Marie-Louise Frémond, Valérie Letscher-Bru, Romain Kessler, Yves Hansmann
Subjects: interstitial lung disease, Lung Diseases, Fungal, [SDV]Life Sciences [q-bio], Immunology, STING GOF, interferon, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, primary immunodeficiency, [SDV] Life Sciences [q-bio], SAVI, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Gain of Function Mutation, Immunology and Allergy, Humans, aspergillosis, Lung, Alleles
Abstract: International audience; No abstract available
Published: 2022
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13. Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to <scp>d</scp>-Dimer Levels

Author: Francis Schneider, Olivier Collange, Aissam Labani, Sébastien Molière, Julie Helms, Mickaël Ohana, François Severac, Xavier Delabranche, Pierre Leyendecker, Ian Leonard-Lorant, Coralie Pauzet, Catherine Roy, Pascal Bilbault, Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération Hospitalo-Universitaire (OMICARE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Hôpital de Hautepierre [Strasbourg], and univOAK, Archive ouverte
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Computed Tomography Angiography, Pneumonia, Viral, 030218 nuclear medicine & medical imaging, Fibrin Fibrinogen Degradation Products, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, D-dimer, Research Letter, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Pandemics, Aged, Retrospective Studies, Original Research, Computed tomography angiography, Aged, 80 and over, medicine.diagnostic_test, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, Confidence interval, Pulmonary embolism, Pneumonia, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Angiography, cardiovascular system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Radiology, Coronavirus Infections, Pulmonary Embolism, business
Abstract: Reports of acute pulmonary embolism associated with coronavirus disease 2019 (COVID-19) have emerged in the literature. For example, Chen et al (1) described 25 pulmonary CT angiographic examinations from 1008 patients with COVID-19; 10 were positive for pulmonary embolism, mostly as segmental or subsegmental acute pulmonary embolism. In addition, d-dimer levels have been reported as elevated in patients with COVID-19 (2,3), with the suggestion of an independent association between the severity of the disease and the level of d-dimer (4). The purpose of this report is to describe the rate of pulmonary embolus in patients classified as having COVID-19 infection who underwent chest CT at a tertiary referral center.
Published: 2020
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14. Clinical characteristics of and outcomes for patients with COVID-19 and comorbid lung diseases primarily hospitalized in a conventional pulmonology unit: A retrospective study

Author: Carole Ederle, Sandrine Hirschi, Eva Chatron, Michele Porzio, Loic Kassegne, Benjamin Renaud-Picard, C. Marcot, Ronald C. Kessler, Tristan Dégot, Pierre Leyendecker, Aissam Labani, Carine Metz-Favre, F. De Blay, Matthieu Canuet, N. Khayath, Marianne Riou, CHU Strasbourg, Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: Lung Diseases, Male, [SDV]Life Sciences [q-bio], Comorbidity, law.invention, pCO2, partial pressure of arterial carbon dioxide, Hospitals, University, 0302 clinical medicine, law, 030212 general & internal medicine, Hospital Mortality, COVID-19, coronavirus disease 2019, NIV, non invasive ventilation, COPD, Continuous Positive Airway Pressure, Smoking, Middle Aged, Intensive care unit, ICU, intensive care unit, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Hospitalization, Intensive Care Units, Pulmonology, medicine.anatomical_structure, Cohort, Hypertension, Female, Original Article, France, Hydroxychloroquine, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, pO2, partial pressure of oxygen, Antibodies, Monoclonal, Humanized, Antiviral Agents, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, RT-PCR, Real-time reverse transcriptase-polymerase chain reaction, 03 medical and health sciences, Sleep Apnea Syndromes, Internal medicine, medicine, Diabetes Mellitus, Humans, Obesity, Risk factor, IQR, interquartile range, Asthma, Aged, Retrospective Studies, Heart Failure, Lung, Noninvasive Ventilation, business.industry, SARS-CoV-2, Oxygen Inhalation Therapy, Anticoagulants, COVID-19, Retrospective cohort study, medicine.disease, ICS, inhaled corticosteroids, respiratory tract diseases, Coronavirus, 030228 respiratory system, COPD, chronic obstructive pulmonary disease, Chronic Disease, ACOS, asthma-COPD overlap syndrome, CPAP, continuous positive airway pressure, business
Abstract: International audience; Background: Scant data are currently available about a potential link between comorbid chronic lung diseases (CLD) and the risk and severity of the coronavirus disease 2019 (COVID-19) infection.Methods: To describe the clinical characteristics of and outcomes for patients with COVID-19 infection, including patients with comorbid respiratory diseases, who have been primarily hospitalized in the pulmonology department of Strasbourg University Hospital, France. In this retrospective, single-center study, we included all confirmed cases of COVID-19 from March 3 to April 15, 2020. We then compared the symptoms, biological and radiological findings, and outcomes for patients with and without CLD.Results: Of the 124 patients that were enrolled, the median age was 62 years, and 75 patients (60%) were male. Overall, 40% of patients (n=50) had preexisting CLD, including chronic obstructive pulmonary disease (COPD) (n=15, 12%) and asthma (n=19, 15%). Twenty-eight patients were transferred to the intensive care unit (ICU), and six patients died in our unit. CLD were not predictive of ICU hospitalization, but a significantly higher total mortality was observed (17.6% vs. 5.5%, P
Published: 2021
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15. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19

Author: Lionel Piroth, Bruno Mourvillier, Joy Mootien, François-Xavier Lescure, Emmanuel Faure, S. Gallien, Dominique Costagliola, Jean-Christophe Richard, Noemie Mercier, Florent Wallet, Yazdan Yazdanpanah, Marion Noret, Claire Andrejak, Jean-Philippe Lanoix, Julien Poissy, Johan Courjon, Saad Nseir, François Danion, Violaine Tolsma, Alain Makinson, Odile Launay, Raphaël Clere-Jehl, Bruno Lina, Drifa Belhadi, Valérie Pourcher, Antoine Kimmoun, Karine Lacombe, Juliette Saillard, Maude Bouscambert-Duchamp, Stéphane Jauréguiberry, Charles Burdet, Toni Alfaiate, Olivier Epaulard, Minh Patrick Lê, Gilles Peytavin, Elisabeth Botelho-Nevers, Thérèse Staub, Guillaume Martin-Blondel, Alpha Diallo, Lila Bouadma, Aline Dechanet, François Goehringer, Florence Ader, Nathan Peiffer-Smadja, Jean-Christophe Navellou, Christelle Delmas, Rostane Gaci, Kevin Bouiller, Maya Hites, André Cabié, Jean Reuter, Sylvie Leroy, Axelle Dupont, François Raffi, Amandine Gagneux-Brunon, Jean Reignier, Clément Dubost, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), 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), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, National Institute for Health Research [Cambridge, UK], Imperial College London, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille, Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Institut de Santé Publique, Université de Médecine Carol Davila, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Réanimation Médicale [CHRU Nancy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de Référence du Paludisme [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), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Les Hôpitaux Universitaires de Strasbourg (HUS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Etablissement français du don du sang [Montpellier], CHU de la Martinique [Fort de France], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université de Paris (UP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Université Lille Nord de France (COMUE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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), 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), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Physiopathologie et biothérapies des infections muqueuses (GIMAP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération d’Infectiologie Multidisciplinaire de l’Arc Alpin [CHU Grenoble-Alpes], Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Institut des Agents Infectieux [Lyon] (IAI), Réseau national de recherche clinique en infectiologie (RENARCI), CHU Amiens-Picardie, Université libre de Bruxelles (ULB), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Lorraine (UL), Hôpital Bicêtre, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Lille, Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université Claude Bernard Lyon 1 (UCBL), 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), 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 Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), CHU Grenoble, Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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 Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (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), 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)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Chrono-environnement (UMR 6249) (LCE), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Lopinavir/ritonavir, law.invention, 0302 clinical medicine, Randomized controlled trial, law, immune system diseases, MESH: Antiviral Agents* / therapeutic use, 030212 general & internal medicine, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, virus diseases, Lopinavir, General Medicine, MESH: Lopinavir / therapeutic use, 3. Good health, Infectious Diseases, MESH: Interferon beta-1a / therapeutic use, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pharmaceutical Preparations, MESH: Hydroxychloroquine / therapeutic use, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, medicine.drug, Hydroxychloroquine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Antiviral Agents, 03 medical and health sciences, Interferon β-1a, Internal medicine, medicine, Humans, education, Adverse effect, MESH: COVID-19* / drug therapy, MESH: Drug Combinations, MESH: Humans, business.industry, SARS-CoV-2, Drug Repositioning, Interferon beta-1a, COVID-19, MESH: Adult, MESH: Male, MESH: Ritonavir / therapeutic use, Ritonavir, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
Published: 2021
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16. High salt exacerbates acute kidney injury by disturbing the activation of CD5L/apoptosis inhibitor of macrophage (AIM) protein

Author: Tetsushi Tezuka, Toru Miyazaki, Kimi Araki, Naoki Takeda, Ching-Ting Wang, Satoko Arai, univOAK, Archive ouverte, The University of Tokyo (UTokyo), Kumamoto University, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GENOMAX [plateforme], and Fédération Hospitalo-Universitaire OMICARE
Subjects: Apoptosis Inhibitor, Exacerbation, Physiology, Test Statistics, Pharmacology, Sodium Chloride, urologic and male genital diseases, Kidney Tubules, Proximal, Mathematical and Statistical Techniques, Blood Flow, Medicine and Health Sciences, Macrophage, Receptors, Scavenger, Mice, Inbred ICR, Multidisciplinary, Statistics, Acute kidney injury, Animal Models, Acute Kidney Injury, female genital diseases and pregnancy complications, Body Fluids, Chemistry, Blood, Experimental Organism Systems, Physical Sciences, Medicine, Female, Anatomy, Research Article, Histology, Science, Ischemia, Mouse Models, Research and Analysis Methods, Model Organisms, Chlorides, medicine, Kidney injury, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Salt intake, Sodium Chloride, Dietary, Statistical Methods, Analysis of Variance, business.industry, urogenital system, Chemical Compounds, Biology and Life Sciences, Kidneys, Renal System, medicine.disease, Animal Studies, Salts, business, Apoptosis Regulatory Proteins, Mathematics, Kidney disease
Abstract: International audience; The influence of excess salt intake on acute kidney injury (AKI) has not been examined precisely except for some clinical data, unlike in chronic kidney disease. Here, we addressed the influence of high salt (HS) on AKI and its underlying mechanisms in terms of the activity of circulating apoptosis inhibitor of macrophage (AIM, also called CD5L) protein, a facilitator of AKI repair. HS loading in mice subjected to ischemia/reperfusion (IR) resulted in high mortality with advanced renal tubular obstruction and marked exacerbation in biomarkers of proximal renal tubular damage. This AKI exacerbation appeared to be caused mainly by the reduced AIM dissociation from IgM pentamer in serum, as IgM-free AIM is indispensable for the removal of intratubular debris to facilitate AKI repair. Injection of recombinant AIM (rAIM) ameliorated the AKI induced by IR/HS, dramatically improving the tubular damage and mouse survival. The repair of lethal AKI by AIM was dependent on AIM/ kidney injury molecule-1 (KIM-1) axis, as rAIM injection was not effective in KIM-1 deficient mice. Our results demonstrate that the inhibition of AIM dissociation from IgM is an important reason for the exacerbation of AKI by HS, that AIM is a strong therapeutic tool for severe AKI.
Published: 2021
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17. selectBoost : a general algorithm to enhance the performance of variable selection methods

Author: Nicolas Jung, Laurent Vallat, Ismail Aouadi, Myriam Maumy-Bertrand, Seiamak Bahram, Raphael Carapito, Frédéric Bertrand, Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Mathématiques, Interactions et Applications (Labex_IRMIA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Laboratoire Modélisation et Sûreté des Systèmes (LM2S), Laboratoire Informatique et Société Numérique (LIST3N), Université de Technologie de Troyes (UTT)-Université de Technologie de Troyes (UTT), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire International Associé (LIA) INSERM, Strasbourg (France) - Nagano (Japan), Strasbourg, France, Université de Technologie de Troyes (UTT), and Bertrand, Frédéric
Subjects: Big Data, Statistics and Probability, AcademicSubjects/SCI01060, Computer science, Big data, Gene Expression, Value (computer science), Context (language use), Feature selection, computer.software_genre, 01 natural sciences, Biochemistry, 010104 statistics & probability, 03 medical and health sciences, [STAT.AP] Statistics [stat]/Applications [stat.AP], Code (cryptography), Sensitivity (control systems), 0101 mathematics, Molecular Biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 030304 developmental biology, Structure (mathematical logic), 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [STAT.ME] Statistics [stat]/Methodology [stat.ME], business.industry, Original Papers, Computer Science Applications, Computational Mathematics, model selection regression classification regularization prediction dimension cancer pls, Computational Theory and Mathematics, Research Design, Data mining, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Algorithms, Software, Biological network, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Motivation With the growth of big data, variable selection has become one of the critical challenges in statistics. Although many methods have been proposed in the literature, their performance in terms of recall (sensitivity) and precision (predictive positive value) is limited in a context where the number of variables by far exceeds the number of observations or in a highly correlated setting. Results In this article, we propose a general algorithm, which improves the precision of any existing variable selection method. This algorithm is based on highly intensive simulations and takes into account the correlation structure of the data. Our algorithm can either produce a confidence index for variable selection or be used in an experimental design planning perspective. We demonstrate the performance of our algorithm on both simulated and real data. We then apply it in two different ways to improve biological network reverse-engineering. Availability and implementation Code is available as the SelectBoost package on the CRAN, https://cran.r-project.org/package=SelectBoost. Some network reverse-engineering functionalities are available in the Patterns CRAN package, https://cran.r-project.org/package=Patterns. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2021
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18. JAK–STAT Targeting Offers Novel Therapeutic Opportunities in Sepsis

Author: Raphaël Clere-Jehl, Seiamak Bahram, Philippe Georgel, Alexandre Mariotte, Julie Helms, Ferhat Meziani, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, multiple organ failure, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, Molecular Targeted Therapy, Molecular Biology, Janus Kinases, signal transducer and activator of transcription, immunosuppression, business.industry, Septic shock, JAK-STAT signaling pathway, Immunosuppression, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], STAT Transcription Factors, 030104 developmental biology, Immunology, STAT protein, Molecular Medicine, Disease Susceptibility, Myelopoiesis, Signal transduction, business, Janus kinase, Biomarkers, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; Sepsis is a life-threatening condition caused by exaggerated host responses to infections taking place in two phases: (i) a systemic (hyper)inflammatory response syndrome (SIRS), participating in multiple organ failure (MOF), a major complication of septic shock, followed by (ii) a compensatory anti-inflammatory response syndrome (CARS), leading to sepsis-induced immunosuppression and resulting in late infections and long-term mortality. The Janus kinase-signal transducer and activator of transcription (JAK-STAT)-dependent signaling pathway is involved in both manifestations, hence playing a key role during sepsis. It is also involved in emergency myelopoiesis, which participates in host defense. The aim of this review is to highlight and refine the recent implications of this signaling pathway in sepsis and illustrate why its central position makes it a potential biomarker and therapeutic target.
Published: 2020
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19. NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation and hyperinflammation Running title: NCKAP1L deficiency

Author: Castro, Carla, Rosenzwajg, Michelle, Carapito, Raphael, Shahrooei, Mohammad, Konantz, Martina, Khan, Amjad, Miao, Zhichao, Gross, Miriam, Tranchant, Thibaud, Radosavljevic, Mirjana, Paul, Nicodème, Stemmelen, Tristan, Pitoiset, Fabien, Hirschler, Aurélie, Nespola, Benoit, Molitor, Anne, Rolli, Véronique, Pichot, Angélique, Faletti, Laura, Rinaldi, Bruno, Friant, Sylvie, Mednikov, Mark, Karauzum, Hatice, Javad Aman, M, CARAPITO, Christine, Lengerke, Claudia, Ziaee, Vahid, Eyaid, Wafaa, Ehl, Stephan, Alroqi, Fayhan, Parvaneh, Nima, Bahram, Seiamak, Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe Plate-forme GENOMAX (Inserm U1109), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Engineering and Technology [Peshawar] (UET), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020
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20. Progress and Challenges in the Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo

Author: Mario P. Tschan, Srinivasa Reddy Bonam, Sylviane Muller, Jagadeesh Bayry, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), 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), University of Bern, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Immuno-pathologie et immuno-intervention thérapeutique = Immunopathology and Therapeutic Immuno-intervention [CRC], 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)-École pratique des hautes études (EPHE), Institut d'Etudes Avancées de l'Université de Strasbourg, Jagadeesh, Bayry, 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)-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), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), and Université de Strasbourg (UNISTRA)
Subjects: autophagy, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Cell, in vivo autophagy assays, 610 Medicine & health, Review, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, autophagic flux, 03 medical and health sciences, In vivo, Lysosome, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, Cellular process, MAP1LC3, 030302 biochemistry & molecular biology, Autophagy, Autophagosomes, A protein, Sciences du Vivant [q-bio]/Biotechnologies, General Medicine, 3. Good health, Cell biology, medicine.anatomical_structure, lcsh:Biology (General), lysosome, 570 Life sciences, biology, Lysosomes, Microtubule-Associated Proteins, Biomarkers, Ex vivo, Intracellular
Abstract: International audience; Tremendous efforts have been made these last decades to increase our knowledge of intracellular degradative systems, especially in the field of autophagy. The role of autophagy in the maintenance of cell homeostasis is well documented and the existence of defects in the autophagic machinery has been largely described in diseases and aging. Determining the alterations occurring in the many forms of autophagy that coexist in cells and tissues remains complicated, as this cellular process is highly dynamic in nature and can vary from organ to organ in the same individual. Although autophagy is extensively studied, its functioning in different tissues and its links with other biological processes is still poorly understood. Several assays have been developed to monitor autophagy activity in vitro, ex vivo, and in vivo, based on different markers, the use of various inhibitors and activators, and distinct techniques. This review emphasizes the methods applied to measure (macro-)autophagy in tissue samples and in vivo via a protein, which centrally intervenes in the autophagy pathway, the microtubule-associated protein 1A/1B-light chain 3 (MAP1LC3), which is the most widely used marker and the first identified to associate with autophagosomal structures. These approaches are presented and discussed in terms of pros and cons. Some recommendations are provided to improve the reliability of the interpretation of results.
Published: 2020
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21. SARS-CoV-2 Pneumonia in Hospitalized Asthmatic Patients Did Not Induce Severe Exacerbation

Author: Frédéric de Blay, Aissam Labani, Julien Godet, Thi Cam Tu Hoang, Carine Metz-Favre, Loic Kassegne, Philippe Fraisse, Benjamin Renaud-Picard, C. Marcot, Ines Abessolo-Amougou, M. Grandbastien, Guillaume Pamart, Samira Fafi-Kremer, Irina Enache, N. Khayath, Virginie Doyen, Pierre Leyendecker, Carole Ederle, Anays Piotin, Louise Manien, Romain Kessler, Marianne Riou, CHU Strasbourg, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: Male, Exacerbation, [SDV]Life Sciences [q-bio], Aucun, Comorbidity, medicine.disease_cause, Severity of Illness Index, law.invention, 0302 clinical medicine, exacerbation, law, immune system diseases, ACE2, Angiotensin Converting Enzyme 2, Immunology and Allergy, 030212 general & internal medicine, Coronavirus, qRT-PCR, quantitative real-time Reverse Transcriptase PCR, Adrenergic beta-Agonists, Middle Aged, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Europe, Intensive Care Units, COVID-19, Coronavirus Disease 2019, Female, France, Coronavirus Infections, medicine.medical_specialty, Pneumonia, Viral, SARS-CoV-2 pneumonia, FEV1, Flow Expiratory Volume in one second, Article, 03 medical and health sciences, Betacoronavirus, Internal medicine, ICU, Intensive Care Unit, Severity of illness, medicine, Humans, FVC, Flow Volume Capacity, Glucocorticoids, Pandemics, Asthma, Aged, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, COPD, Chronic Obstructive Pulmonary Disease, asthma, medicine.disease, Respiration, Artificial, respiratory tract diseases, Pneumonia, SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2, 030228 respiratory system, Socioeconomic Factors, BMI, Body Mass Index, business
Abstract: Background Viral infections are known to exacerbate asthma in adults. Previous studies have found few asthmatics among SARS-CoV-2 pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known. Objective We assessed the frequency of asthma exacerbation in asthmatic patients hospitalized for SARS-CoV-2 pneumonia and compared symptoms laboratory and radiological findings in asthmatic and non-asthmatic patients with SARS-CoV-2 pneumonia. Methods We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 were asthmatics. To assess the patients’ asthma status, three periods were defined: the last month before the onset of COVID-19 symptoms (p1), pre-hospitalization (p2) and during hospitalization (p3). Severe asthma exacerbations were defined according to GINA guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled beta-2-agonist. Results We found no significant difference between asthmatics and non-asthmatics in terms of severity (length of stay, maximal oxygen flow needed, non-invasive ventilation requirement and ICU transfer). 52.2% of the asthmatic patients were Gina 1. One patient had a severe exacerbation during p1, two patients during p2, and five patients were treated with systemic corticosteroids and inhaled beta-2-agonist during p3. Conclusion Our results demonstrate that asthmatic patients appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation., Highlights box: 1. What is already known about this topic? Asthmatic patients are rare in epidemiological studies of SARS-CoV-2 pneumonia. 2. What does this article add to our knowledge? Being asthmatic is not a risk factor for severe SARS-CoV-2. 3. How does this study impact current management guidelines? SARS-CoV-2 pneumonia may not induce severe asthma exacerbation.
Published: 2020
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22. Temporomandibular Joint Damage in K/BxN Arthritic Mice

Author: Sabine, Kuchler-Bopp, Alexandre, Mariotte, Marion, Strub, Chrystelle, Po, Aurore, De Cauwer, Georg, Schulz, Xavier, Van Bellinghen, Florence, Fioretti, François, Clauss, Philippe, Georgel, Nadia, Benkirane-Jessel, Fabien, Bornert, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University of Basel (Unibas), and univOAK, Archive ouverte
Subjects: musculoskeletal diseases, Temporomandibular Joint, Mice, Transgenic, X-Ray Microtomography, Arthritis, Experimental, Magnetic Resonance Imaging, Bone and Bones, Article, Arthritis, Rheumatoid, lcsh:RK1-715, Disease Models, Animal, Mice, Matrix Metalloproteinase 8, Animal disease models, lcsh:Dentistry, Animals, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rheumatoid arthritis, Tomography, X-Ray Computed
Abstract: Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/BxN mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint (TMJ) inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging (μMRI) and micro-computed tomography (μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/BxN animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes (FLSs) isolated from the TMJ of K/BxN mice secreted inflammatory cytokines (IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases (MMPs). K/BxN mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.
Published: 2020
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23. COVID-19: what the clinician should know about post-mortem findings

Author: Julie Helms, Danny Jonigk, Bruno Märkl, univOAK, Archive ouverte, Hannover Medical School [Hannover] (MHH), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Clinic for Paediatric Pneumology and Neonatology, University of Augsburg (UNIA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], and University of Augsburg [Augsburg]
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Respiratory Distress Syndrome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Coronavirus disease 2019 (COVID-19), business.industry, Pain medicine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, COVID-19, 030208 emergency & critical care medicine, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Editorial, Anesthesiology, Emergency medicine, medicine, Humans, Autopsy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: No abstract available
Published: 2020
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24. Genes-Basel

Author: Amjad Khan, Mohammad A Alshabeeb, Amir Ullah, Gudrun A. Rappold, Raphael Carapito, Muhammad Umair, Muhammad Ansar, Farooq Ahmad, Zhichao Miao, Muhammad Bilal, GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, Immuno-Rhumatologie Moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: 0301 basic medicine, METTL23, lcsh:QH426-470, In silico, autosomal recessive intellectual disability ndst1 mettl23 exome sequencing genetics mutations, NDST1, Case Report, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, 030105 genetics & heredity, Biology, Genetic Condition, autosomal recessive intellectual disability, 03 medical and health sciences, symbols.namesake, Intellectual disability, Genetics, medicine, Homology modeling, Gene, Genetics (clinical), Exome sequencing, Brain function, Sanger sequencing, medicine.disease, lcsh:Genetics, 030104 developmental biology, symbols, exome sequencing, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.
Published: 2020
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25. Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Author: Su, Bin, Dispinseri, Stefania, Iannone, Valeria, ZHANG, Tong, Wu, Hao, Carapito, Raphael, Bahram, Seiamak, Scarlatti, Gabriella, Moog, Christiane, Capital University of Medical Sciences [Beijing] (CUMS), San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Vaccine Research Institute (VRI), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: AIDS Vaccines, Immunology, non-neutralizing antibodies, Antibody-Dependent Cell Cytotoxicity, HIV Infections, Review, HIV Antibodies, FcR-mediated inhibition, Antibodies, Neutralizing, Immunoglobulin Fc Fragments, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, ADCC, antibody functions
Abstract: Antibodies (Abs) are the major component of the humoral immune response and a key player in vaccination. The precise Ab-mediated inhibitory mechanisms leading to in vivo protection against HIV have not been elucidated. In addition to the desired viral capture and neutralizing Ab functions, complex Ab-dependent mechanisms that involve engaging immune effector cells to clear infected host cells, immune complexes, and opsonized virus have been proposed as being relevant. These inhibitory mechanisms involve Fc-mediated effector functions leading to Ab-dependent cellular cytotoxicity, phagocytosis, cell-mediated virus inhibition, aggregation, and complement inhibition. Indeed, the decreased risk of infection observed in the RV144 HIV-1 vaccine trial was correlated with the production of non-neutralizing inhibitory Abs, highlighting the role of Ab inhibitory functions besides neutralization. Moreover, Ab isotypes and subclasses recognizing specific HIV envelope epitopes as well as pecular Fc-receptor polymorphisms have been associated with disease progression. These findings further support the need to define which Fc-mediated Ab inhibitory functions leading to protection are critical for HIV vaccine design. Herein, based on our previous review Su & Moog Front Immunol 2014, we update the different inhibitory properties of HIV-specific Abs that may potentially contribute to HIV protection.
Published: 2019
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26. The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1

Author: Mar Pérez-Ruiz, Juan García-Arriaza, Carlos Oscar S. Sorzano, Christiane Moog, César Santiago, Rogier W. Sanders, Aneesh Vijayan, Mariano Esteban, Ernesto Mejías-Pérez, Ana Maria Cuervo, Cristina Sánchez-Corzo, Beatriz Perdiguero, Suresh C. Raman, José L. Carrascosa, Anna Schorcht, Judith A. Burger, Carmen E. Gómez, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), University of Amsterdam [Amsterdam] (UvA), Weill Medical College of Cornell University [New York], univOAK, Archive ouverte, Instituto de Salud Carlos III, Medical Microbiology and Infection Prevention, AII - Infectious diseases, and Graduate School
Subjects: 0301 basic medicine, HIV-1 neutralizing antibodies, viruses, T-Lymphocytes, HIV Antibodies, HIV Envelope Protein gp120, Mice, GP120C14K, MVA-HIV vaccine, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, Neutralizing antibody, Original Research, AIDS Vaccines, Mice, Inbred BALB C, biology, Chemistry, Immunogenicity, virus diseases, 3. Good health, medicine.anatomical_structure, Female, Rabbits, Antibody, VACV 14K protein, Tfh cells, lcsh:Immunologic diseases. Allergy, T cell, Recombinant Fusion Proteins, Immunology, Vaccinia virus, CD8 T cells, CHO Cells, complex mixtures, 03 medical and health sciences, Viral Proteins, Cricetulus, Antigen, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, B cell, SOSIPs, Virology, Fusion protein, Antibodies, Neutralizing, 030104 developmental biology, biology.protein, HIV-1, Immunization, GC B cells, lcsh:RC581-607, 030215 immunology
Abstract: There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1). Here, we describe the generation and characterization of a fusion antigen comprised of the HIV-1 envelope GP120 glycoprotein from clade C (GP120C) fused at its C-terminus, with the modified vaccinia virus (VACV) 14K protein (A27L gene) (termed GP120C14K). The design is directed toward improving the immunogenicity of the GP120C protein through its oligomerization facilitated by the fused VACV 14K protein that results in hexamer-like structures. Two different immunogens were generated: a recombinant GP120C14K fusion protein (purified from a stable CHO-K1 cell line) and a recombinant modified vaccinia virus Ankara (MVA) poxvirus vector expressing the GP120C14K fusion protein (termed MVA-GP120C14K). The GP120C14K fusion protein is recognized by broadly neutralizing antibodies (bNAbs) against HIV-1. In a murine model, a heterologous prime/boost immunization regimen with MVA-GP120C14K prime followed by adjuvanted GP120C14K protein boost generated stronger and polyfunctional HIV-1 Env-specific CD8 T cell responses when compared with the delivery of the monomeric GP120C form. Furthermore, the immunization protocol MVA-GP120C14K/GP120C14K elicited higher HIV-1 Env-specific T follicular helper cells, germinal center B cells and antibody responses than monomeric GP120. In addition, a similar MVA-GP120C14K prime/GP120C14K protein boost regimen performed in rabbits triggered high HIV-1-Env-specific IgG binding antibody titers that were capable of neutralizing HIV-1 pseudoviruses. The extent of HIV-1 neutralization was comparable to that elicited by the current standard GP140 SOSIP trimers from clades B and C when immunized as MVA-SOSIP prime/SOSIP protein boost regimen. Overall, the novel fusion antigen and the corresponding immunization scheme provided in this report can therefore be considered as potential vaccine strategies against HIV-1., This investigation was supported by Spanish grants SAF201345232R and SAF-2017-88089R and, in part, by EU H2020 EHVA grant REP-681032-2. This research was also supported by Spanish AIDS Research Network RD16/0025/0014-ISCIII – FEDER
Published: 2019
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27. Systemic lupus erythematosus and neutropaenia: a hallmark of haematological manifestations

Author: Aurore, Meyer, Aurélien, Guffroy, Gilles, Blaison, Yannick, Dieudonne, Zahir, Amoura, Bernard, Bonnotte, Christoph, Fiehn, Pierre, Kieffer, Hannes Martin, Lorenz, Nadine, Magy-Bertrand, François, Maurier, Jean-Louis, Pennaforte, Hans-Hartmut, Peter, Andreas, Schwarting, Jean, Sibilia, Laurent, Arnaud, Thierry, Martin, Reinhard Edmund, Voll, Anne-Sophie, Korganow, R, Voll, CHU Strasbourg, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Heidelberg University Hospital [Heidelberg], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpitaux Privés de Metz (HPMetz), Centre Hospitalier Universitaire de Reims (CHU Reims), University of Freiburg [Freiburg], Les Hôpitaux Universitaires de Strasbourg (HUS), and LBBR/Rarenet group: Z Amoura, L Arnaud, G Blaison, B Bonnotte, E Chatelus, E Ciobanu, F Duchene, J P Faller, A Gorse, J E Gottenberg, O Hinschberger, F Jaeger, P Kieffer, M Kilifa, N Magy-Bertrand, T Martin, L Martzolff, F Maurier, A Meyer, J-L Pasquali, J-L Pennaforte, V Poindron, S Revuz, M Samson, J Sibilia, C Sordet, A Theulin, D Wahl, J C Weber, M Bartsch, N Bartholomä, C Fiehn, S Finzel, A Funkert, M Hausberg, H Lorenz, R Max, H-H Peter, M Rizzi, A Schwarting, J Thiel, N Venhoff, R Voll
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Neutropenia, autoantibodies, Immunology, Disease, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Germany, Lymphopenia, lupus erythematosus, systemic, Internal medicine, medicine, Humans, Oral ulcers, 030203 arthritis & rheumatology, Autoimmune disease, Systemic lupus erythematosus, Genetic heterogeneity, business.industry, Autoantibody, Complement C3, General Medicine, systemic, medicine.disease, Thrombocytopenia, Epidemiology and Outcomes, 3. Good health, Cross-Sectional Studies, Sjogren's Syndrome, 030104 developmental biology, Antibodies, Antinuclear, Case-Control Studies, Cohort, Absolute neutrophil count, Female, France, business, lupus erythematosus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveSystemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%–40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined.Methods998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×106/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia.Results208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57–10.3)), lymphopaenia (OR 4.41 (2.51–11.5)) and low C3 (OR 1.91 (1.03–4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers.ConclusionThis study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren’s disease.
Published: 2020
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28. Transitional B cells in quiescent SLE: An early checkpoint imprinted by IFN

Author: Jennifer L. Barnas, Anna K. Bird, Anne-Sophie Korganow, Thierry Martin, Jane L. Liesveld, Vincent Gies, Pauline Soulas-Sprauel, Eric Meffre, Vincent Poindron, N. Douiri, Yannick Dieudonné, Céline Keime, Aurélien Guffroy, Jennifer H. Anolik, CCSD, Accord Elsevier, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Rochester Medical Center (URMC), University of Rochester [USA], Yale School of Medicine [New Haven, Connecticut] (YSM), and Yale University School of Medicine
Subjects: Adult, 0301 basic medicine, Antigens, CD19, Immunology, Naive B cell, B-Lymphocyte Subsets, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, CD19, Sciences du Vivant [q-bio]/Génétique, 03 medical and health sciences, TLR9, 0302 clinical medicine, Systemic lupus erythematosus, Downregulation and upregulation, Interferon, Sciences du Vivant [q-bio]/Biologie cellulaire, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Sciences du Vivant [q-bio]/Immunologie, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, B cell, Aged, Autoantibodies, 030203 arthritis & rheumatology, Precursor Cells, B-Lymphoid, Transitional B cells, Autoantibody, Middle Aged, 030104 developmental biology, medicine.anatomical_structure, Toll-Like Receptor 9, biology.protein, Female, Interferons, Bone marrow, Transcriptome, medicine.drug
Abstract: Systemic lupus (SLE) is characterized by a break of B cell tolerance that plays a central role in disease pathophysiology. An early checkpoint defect occurs at the transitional stage leading to the survival of autoreactive B cells and consequently the production of pathogenic autoantibodies. The main purpose of our work was to determine whether transitional B cells, as the most immature naïve B cell subset upstream of pathogenic B cells, display specific features compared to healthy non SLE subjects. Through extensive analysis of transitional B cells from untreated or low treated, mostly Caucasian, SLE patients, we demonstrated that transitional (T1 and T2) B cell frequencies were increased in SLE and positively correlated with disease activity. SLE transitional B cells displayed defects in two closely inter-related molecules (i.e. TLR9 defective responses and CD19 downregulation). RNA sequencing of sorted transitional B cells from untreated patients revealed a predominant overexpression of interferon stimulated genes (ISGs) even out of flares. In addition, early transitional B cells from the bone marrow displayed the highest interferon score, reflecting a B cell interferon burden of central origin. Hence, the IFN signature in transitional B cells is not confined to African American SLE patients and exists in quiescent disease since the medullary stage. These results suggest that in SLE these 3 factors (i.e. IFN imprintment, CD19 downregulation and TLR9 responses impairment) could take part at the early transitional B cell stage in B cell tolerance by-pass, ultimately leading in periphery to the expansion of autoantibodies-secreting cells.
Published: 2019
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29. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis

Author: Steven Gazal, Hilario Nunes, Jean Sibilia, Christelle Ménard, Aurélien Justet, Philippe Dieudé, Isabelle Callebaut, Amélie Bonnefond, Martin Soubrier, Patrick Revy, Catherine Boileau, Pierre-Antoine Juge, Thierry Schaeverbeke, Aline Frazier, Nathalie Saidenberg, Sébastien Ottaviani, Nadia Nathan, Bruno Crestani, Christophe Béroud, Baptiste Coustet, Vincent Cottin, Lidwine Wemeau-Stervinou, Jean-Pierre Desvignes, Marie-Christophe Boissier, Florence Dastot-Le Moal, Serge Amselem, Philippe Froguel, Yannick Allanore, Annick Clement, Olivier Sand, Gabriel Thabut, Marie-Pierre Debray, Pascal Richette, Caroline Kannengiesser, Benoit Wallaert, Christophe Richez, Dominique Valeyre, Sylvain Marchand-Adam, Huguette Lioté, Nicolas Leulliot, René-Marc Flipo, Raphael Borie, Claire Dromer, David Salgado, Service de Rhumathologie, Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), UMR 1152, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), UMR 1149, Centre de Recherches sur l'Inflammation, Ecologie et Ecophysiologie Forestières [devient SILVA en 2018] (EEF), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Plateforme de génomique constitutionnelle, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Service de Radiologie, Hospices Civils de Lyon (HCL), UMR 1100, Université Francois Rabelais [Tours], Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie, CH Belfort-Montbéliard, UMR 5164, Immuno ConcEpT Lab, Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Sorbonne Université (SU), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD [France-Ouest]), Muséum national d'Histoire naturelle (MNHN), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université de Lille, Droit et Santé, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UMR 1132, Service de Rhumatologie, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Department of Genomics of Common Diseases, Imperial College London, Service Rhumatologie A, Hôpital Cochin [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), Service Imagerie, service de Rhumatologie, Centre Hospitalier Universitaire de Lille (CHU de Lille), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Rhumatologie, Hôpital La Rabta [Tunis], FMTS, CRHI, Laboratoire Immunologie Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire OMICARE, Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Maladie Pulmonaires Rares, Hôpital Louis Pradel [CHU - HCL], UMR U1125 Service rhumatologie, service de rhumatologie, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Hôpital Avicenne [AP-HP], service de génétique, Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris France, ANR-14-CE10-0006,GENEXGERTEL,Rôles génomiques et extragénomiques de RTEL1(2014), Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Université Paris Diderot (Paris 7), Université Sorbonne Paris Cité ( USPC ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Saint-Etienne, UMR 1137, Fac Sci, 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 National de la Recherche Scientifique ( CNRS ), Service de Pneumologie et Immuno-Allergologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ), Service de Pneumologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie (Paris 6), Centre National de la Recherche Scientifique ( CNRS ), Université de Bordeaux ( UB ), Sorbonne Universités, Institut de minéralogie, de physique des matériaux et de cosmochimie ( IMPMC ), Muséum National d'Histoire Naturelle ( MNHN ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche pour le Développement ( IRD [France-Ouest] ), Muséum National d’Histoire Naturelle ( MNHN ), Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Droit et Santé (Lille 2) ( UDSL ), European Genomic Institute for Diabetes ( EGID ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Lariboisière, Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Cochin [AP-HP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Hôpital La Rabta [Tunis), Université de Strasbourg ( UNISTRA ), Rétrovirus et Pathologie Comparée ( RPC ), Institut National de la Recherche Agronomique ( INRA ) -École pratique des hautes études ( EPHE ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon ( ENVL ), Département Génétique, Institut de l'Elevage, Centre Reference Maladies Respiratoires Rares, Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Centre de Recherche en Nutrition Humaine d'Auvergne ( CRNH d'Auvergne ), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris ( AP-HP ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Institut de l'élevage (IDELE), ProdInra, Archive Ouverte, Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie 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)-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), Service de génétique et embryologie médicales [CHU Trousseau], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), European Genomic Institute for Diabetes [Lille] (EGID), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris (AP-HP), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.disease_cause, Arthritis, Rheumatoid, 0302 clinical medicine, Risk Factors, Pulmonary fibrosis, Exome, Telomerase, Exome sequencing, Mutation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Interstitial lung disease, Middle Aged, 3. Good health, Europe, Polyarthrite rhumatoïde, maladie pulmonaire, Phenotype, Rheumatoid arthritis, Female, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Heterozygote, fibrose pulmonaire, 03 medical and health sciences, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, respiratory system diseases, Genetic Association Studies, Aged, 030203 arthritis & rheumatology, pulmonary fibrosis, business.industry, Case-control study, DNA Helicases, Sequence Analysis, DNA, medicine.disease, 030228 respiratory system, Case-Control Studies, Immunology, business, Lung Diseases, Interstitial, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
Published: 2017
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30. Whole genome sequencing of 7 strains of Staphylococcus lugdunensis allows identification of mobile genetic elements

Author: Xavier Argemi, Mickael Martin, Nicodème Paul, Gilles Prévost, Véronique Martin, Valentin Loux, Aurélie Velay, Yves Hansmann, Sandrine Dahyot, Philippe Riegel, Jérémie Lebeurre, Daniel Keller, A. Guffroy, Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), CHU Strasbourg, Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de la Recherche Agronomique (INRA), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Immunopathologie et Chimie Thérapeutique/Equipe, Tolérance Cellulaire B et Auto-immunité, Centre National de la Recherche Scientifique (CNRS), Centre de recherche du médicament Medalis - Drug Discovery Center [LabEx], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, Centre Hospitalier Régional Universitaire de Strasbourg (CHRU de Strasbourg), Institut de bactériologie, Fédération de Médecine Translationelle de Strasbourg (FMTS), Maladies Infectieuses et Tropicales, Hôpitaux Universitaires, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Laboratoire d'excellence Medalis, Institut de Biologie Moléculaire et Cellulaire (IBMC), Service d'Immunologie Clinique et de Médecine Interne - Centre National de Référence des Maladies Auto-immunes Rares, Institute of Molecular and Cellular Biology, Virology Laboratory, General Hospital Papageorgiou, UMR S1109, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'ImmunoRhumatologie Moléculaire, and plateforme GENOMAX
Subjects: 0301 basic medicine, plasmids, [SDV]Life Sciences [q-bio], Virulence, Staphylococcus lugdunensis, Staphylococcal infections, Genome, Microbiology, 03 medical and health sciences, Plasmid, prophages, Genetics, medicine, Ecology, Evolution, Behavior and Systematics, Prophage, Whole genome sequencing, next generation sequencing, biology, biology.organism_classification, medicine.disease, 3. Good health, virulence, 030104 developmental biology, Mobile genetic elements
Abstract: Coagulase negative staphylococci are normal inhabitant of the human skin flora that account for an increasing number of infections, particularly hospital-acquired infections. Staphylococcus lugdunensis has emerged as a most virulent species causing various infections with clinical characteristics close to what clinicians usually observe with Staphylococcus aureus and both bacteria share more than 70% of their genome. Virulence of S. aureus relies on a large repertoire of virulence factors, many of which are encoded on mobile genetic elements. S. lugdunensis also bears various putative virulence genes but only one complete genome with extensive analysis has been published with one prophage sequence (φSL2) and a unique plasmid was previously described. In this study, we performed de novo sequencing, whole genome assembly and annotation of seven strains of S. lugdunensis from VISLISI clinical trial. We searched for the presence of virulence genes and mobile genetics elements using bioinformatics tools. We identified four new prophages, named φSL2 to φSL4, belonging to the Siphoviridae class and five plasmids, named pVISLISI_1 to pVISLISI_5. Three plasmids are homologous to known plasmids that include, amongst others, one S. aureus plasmid. The two other plasmids were not described previously. This study provides a new context for the study of S. lugdunensis virulence suggesting the occurrence of several genetic recombination' with other staphylococci.
Published: 2017
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31. The TRANSPLANTEX initiative

Author: Pierre-Antoine Gourraud, Dominique Charron, Seiamak Bahram, Raphael Carapito, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg] (FJ-HLA), Laboratoire International Associé (LIA), Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Pôle de Biologie - Laboratoire d’Immunologie [Nouvel Hôpital Civil, Strasbourg] (Plateau Technique de Biologie), Nouvel Hôpital Civil - NHC [Strasbourg], 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), Department of Neurology [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California, LabEx TRANSPLANTEX [CHU de Nantes], HLA & Médecine ‘‘Jean Dausset' Laboratory Network [Hôpital Saint-Louis - APHP] (LabEx TRANSPLANTEX), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rujin Hospital Shanghai [Shanghai, China], Shanghai Jiao Tong University [Shanghai], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Le Bihan, Sylvie, University of California [San Francisco] (UC San Francisco), and University of California (UC)-University of California (UC)
Subjects: 0301 basic medicine, Graft Rejection, medicine.medical_specialty, Consensus, Immunology, Aucun, Graft vs Host Disease, diagnosis, therapy, Histocompatibility Testing, Disease, 03 medical and health sciences, 0302 clinical medicine, prevention & control, medicine, Immunology and Allergy, Humans, Registries, Intensive care medicine, Kidney transplantation, Immunosuppression Therapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hematopoietic cell, business.industry, General Medicine, medicine.disease, Omics, Kidney Transplantation, Post transplant, 3. Good health, Histocompatibility, Chronic graft rejection, 030104 developmental biology, France, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: TRANSPLANTEX, a French "investment for the future" initiated consortium of leading transplant units and research laboratories across France and a number of European countries aims to unravel, through mainly high-throughput genomics (and other omics) analyses of donor and recipients, novel (a) non-HLA, histocompatibility antigens, whether inside, or outside the MHC; (b) pre/post transplantation biomarkers. This shall lead to our better understanding of the pathophysiology of (and eventually designing better therapeutics for) the graft-versus-host disease in hematopoietic cell transplants and that of chronic graft rejection after kidney transplant. Industrial developments as well as innovative teaching initiatives are also integral part of this program. The present issue of Human Immunology aims to present a first snapshot of some of the research performed by TRANPLANTEX partners. editorial 2016 Nov imported
Published: 2016
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32. Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism.

Author: Arbogast F, Sal-Carro R, Boufenghour W, Frenger Q, Bouis D, Filippi De La Palavesa L, Fauny JD, Griso O, Puccio H, Fima R, Huby T, Gautier EL, Molitor A, Carapito R, Bahram S, Romani N, Clausen BE, Voisin B, Mueller CG, Gros F, and Flacher V
Subjects: Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria metabolism, Langerhans Cells metabolism, Autophagy, Lipid Metabolism, Epidermis metabolism, Autophagy-Related Protein 7 genetics, Autophagy-Related Protein 7 metabolism, Autophagy-Related Protein 5 metabolism, Autophagy-Related Protein 5 genetics
Abstract: Macroautophagy (often-named autophagy), a catabolic process involving autophagy-related (Atg) genes, prevents the accumulation of harmful cytoplasmic components and mobilizes energy reserves in long-lived and self-renewing cells. Autophagy deficiency affects antigen presentation in conventional dendritic cells (DCs) without impacting their survival. However, previous studies did not address epidermal Langerhans cells (LCs). Here, we demonstrate that deletion of either Atg5 or Atg7 in LCs leads to their gradual depletion. ATG5-deficient LCs showed metabolic dysregulation and accumulated neutral lipids. Despite increased mitochondrial respiratory capacity, they were unable to process lipids, eventually leading them to ferroptosis. Finally, metabolically impaired LCs upregulated proinflammatory transcripts and showed decreased expression of neuronal interaction receptors. Altogether, autophagy represents a critical regulator of lipid storage and metabolism in LCs, allowing their maintenance in the epidermis., (© 2024 Arbogast et al.)
Published: 2025
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33. Evolution of anti-MICA antibodies after imlifidase infusion for a high immunological risk kidney transplantation.

Author: Beaudrey T, Apithy MJ, Olagne J, Lemonnier L, Perrin P, Vargas GG, Jahn I, Radosavljevic M, Bahram S, Carapito R, and Caillard S
Abstract: Imlifidase is an endopeptidase known for cleaving anti-Human Leucocyte Antigen donor-specific antibodies (DSA) to allow high-risk kidney transplantation. However, it lacks comprehensive data regarding its effect on alloantibodies targeting other histocompatibility antigens, such as Major Histocompatibility Complex class I chain-related protein A (MICA). This study describes the dynamics of anti-MICA antibodies following imlifidase administration in a kidney transplant recipient with anti-MICA*002 preformed DSA. Imlifidase induced a notable reduction in anti-MICA antibodies, followed by a rebound of the anti-MICA DSA after 14 days. Subsequent to early antibody-mediated rejection, the combination of immunoadsorption and daratumumab infusion proved effective in removing all anti-MICA antibodies at day 45 after transplantation. These findings shed light on the management of anti-MICA antibodies, an area still lacking consensus in current clinical practice. This research underscores the significance of imlifidase in addressing pretransplant anti-MICA and other antibodies directed against non-HLA targets, extending its therapeutic utility in kidney transplantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2025
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34. Release of apoptosis inhibitor of macrophage (AIM) from pentameric IgM in serum predicts prognosis after hemodialysis initiation.

Author: Yasuda K, Nishijima A, Inoue T, Takagi T, Tanabe K, Minakuchi J, Arai S, and Miyazaki T
Abstract: Background: The optimal timing for initiating dialysis and prognostic markers in chronic kidney disease (CKD) patients are under debate, with mortality and cardiovascular risks varying among patients. This study investigates whether the apoptosis inhibitor of macrophage (AIM), which is mostly bound to pentameric IgM, could serve as an effective indicator., Methods: We prospectively followed 423 patients at dialysis initiation and 563 at various CKD stages. AIM dissociation from IgM and other serum components were measured in their serum samples. In vitro treatment of IgM-AIM complexes with their serum was conducted to assess AIM release from IgM. Survival analysis determined the associations of each variable with mortality and cardiovascular risk, and a cutoff value was calculated and validated using cross-validation., Results: AIM dissociation from IgM increases with CKD progression and correlates with the serum uremic state, as shown by enhanced AIM release from IgM in vitro with sera from patients starting dialysis, but not those at earlier CKD stages. Patients at dialysis initiation with high proportion of serum IgM-free AIM (fAIM%) show elevated uremic toxins and other toxic metabolites, higher mortality, and increased cardiovascular risk compared to those with low fAIM%. This prognostic association is not seen with other CKD biomarkers, such as eGFR, creatinine, or inositol-phosphate. We determined the fAIM% cutoff of 46.27%, which predicts mortality two years post-dialysis initiation., Conclusions: These findings suggest that the serum fAIM% could function as a prognostic marker at dialysis initiation and may have potential as a criterion for determining dialysis timing., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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35. Prevalence rate of high-grade cytological lesions of the cervix in women aged under 25 years in French Guiana.

Author: Heckmann PA, Collin-Bund V, Thomas N, Alsibai KD, Ehrhardt A, Quet F, Akladios C, and Lecointre L
Abstract: Introduction: The incidence of cervical cancer in French Guiana is among the highest worldwide. It ranks 5th among all cancers and is the 2nd most common cancer in women after breast cancer. The primary objective of this study was to establish the proportion of high-grade cytological lesions of the cervix in women under 25 years of age who underwent a cervico-uterine smear (CUS) in French Guiana over a 10-year period., Material and Methods: This cross-sectional, retrospective, and descriptive study included all female patients under 25 years of age who underwent CUS between January 1, 2010, and December 31, 2019, in French Guiana, regardless of the reason for consultation., Results: A total of 17,275 CUS were selected for analysis of the results and study of squamous abnormalities, of which 15,421 (89.3%) showed no abnormality, and 1,854 (10.7%) showed a squamous abnormality. Only 3.9% of patients presented with atypical squamous cell evocating high grade lesions and 4.4% with high-grade squamous intraepithelial lesions. The prevalence and severity of the abnormalities increased with age; no cases of cancers were detected., Conclusion: In view of the results and the benefit/risk balance, systematic generalized early screening for those aged 25 and over does not appear to be warranted. Instead, screening should be targeted based on clinical history., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
Published: 2025
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36. RICTOR variants are associated with neurodevelopmental disorders.

Author: Carapito R, Molitor A, Pavinato L, Skeyni A, Lambert M, Pichot A, Jiang J, Spinnhirny P, Zimmermann L, Boucher P, Chung CWT, Elserafy N, Blair EM, Li D, Elisabeth B, Kotzaeridou U, Karch S, Wagner M, Lunsing RJ, Pfundt R, Boycott KM, Bruel AL, Mau-Them FT, Moutton S, Conti V, Mei D, Cetica V, Guerrini R, Brunet T, Rump P, Mussa A, Brusco A, Lemire G, de Vries BBA, Miao Z, Isidor B, and Bahram S
Abstract: RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene. The phenotypic presentation is diverse with associated features including growth failure, feeding difficulties, abnormal behavior, seizure, hypertonia, brain anomalies and various other congenital organ and skeletal malformations. All patients carried de novo or heterozygous variants inherited from one affected parent, including three missense variants, four loss-of-function variants and one 3 kb deletion encompassing RICTOR. The mTORC2 pathway was hyperactivated in a patient's fibroblasts carrying a missense variant, while the expression of RICTOR remained unchanged, indicating a gain-of-function mechanism. RNA sequencing on RICTOR knock-out mouse embryonic fibroblasts confirmed the potential role of RICTOR in neuronal cell development., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: All sequencing experiments were performed upon written informed consent for clinical sequencing and/or by center-specific institutional review board approval for research sequencing., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)
Published: 2024
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37. Endothelial calcium firing mediates the extravasation of metastatic tumor cells.

Author: Peralta M, Dupas A, Larnicol A, Lefebvre O, Goswami R, Stemmelen T, Molitor A, Carapito R, Girardo S, Osmani N, and Goetz JG
Abstract: Metastatic dissemination is driven by genetic, biochemical, and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrapping arrested tumor cells (TCs) and extruding them from the vascular lumen while maintaining perfusion. In this work, we dissect the cellular and molecular mechanisms driving endothelial remodeling. Using high-resolution intravital imaging in zebrafish embryos, we demonstrate that the actomyosin network of ECs controls tissue remodeling and subsequent TC extravasation. Furthermore, we uncovered that this cytoskeletal remodeling is driven by altered endothelial-calcium (Ca 2+ ) signaling caused by arrested TCs. Accordingly, we demonstrated that the inhibition of voltage-dependent calcium L-type channels impairs extravasation. Lastly, we identified P2X4, TRP, and Piezo1 mechano-gated Ca 2+ channels as key mediators of the process. These results further highlight the central role of endothelial remodeling during the extravasation of TCs and open avenues for successful therapeutic targeting., Competing Interests: The authors declare no competing interests., (© 2025 The Authors. Published by Elsevier Inc.)
Published: 2024
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38. Defective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome.

Author: Dieudonné Y, Lorenzetti R, Rottura J, Janowska I, Frenger Q, Jacquel L, Vollmer O, Carbone F, Chengsong Z, Luka M, Depauw S, Wadier N, Giorgiutti S, Nespola B, Herb A, Voll RE, Guffroy A, Poindron V, Ménager M, Martin T, Soulas-Sprauel P, Rizzi M, Korganow AS, and Gies V
Subjects: Humans, Female, Adult, Middle Aged, Male, Antibodies, Antiphospholipid immunology, Receptors, Antigen, B-Cell metabolism, Receptors, Antigen, B-Cell immunology, Single-Cell Analysis, Autoantibodies immunology, Aged, Germinal Center immunology, Antiphospholipid Syndrome immunology, B-Lymphocytes immunology
Abstract: Primary antiphospholipid syndrome (PAPS) is a life-threatening clotting disorder mediated by pathogenic autoantibodies. Here we dissect the origin of self-reactive B cells in human PAPS using peripheral blood and bone marrow of patients with triple-positive PAPS via combined single-cell RNA sequencing, B cell receptors (BCR) repertoire profiling, CITEseq analysis and single cell immortalization. We find that antiphospholipid (aPL)-specific B cells are present in the naive compartment, polyreactive, and derived from the natural repertoire. Furthermore, B cells with aPL specificities are not eliminated in patients with PAPS, persist until the memory and long-lived plasma cell stages, likely after defective germinal center selection, while becoming less polyreactive. Lastly, compared with the non-PAPS cells, PAPS B cells exhibit distinct IFN and APRIL signature as well as dysregulated mTORC1 and MYC pathways. Our findings may thus elucidate the survival mechanisms of these autoreactive B cells and suggest potential therapeutic targets for the treatment of PAPS., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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39. Machine learning for precision diagnostics of autoimmunity.

Author: Kruta J, Carapito R, Trendelenburg M, Martin T, Rizzi M, Voll RE, Cavalli A, Natali E, Meier P, Stawiski M, Mosbacher J, Mollet A, Santoro A, Capri M, Giampieri E, Schkommodau E, and Miho E
Subjects: Humans, Autoimmunity, Precision Medicine methods, Decision Support Systems, Clinical, Machine Learning, Autoimmune Diseases diagnosis, Autoimmune Diseases immunology
Abstract: Early and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions., Competing Interests: D eclarations Conflict of interest Jan Kruta, Raphael Carapito, Marten Trendelenburg, Thierry Martin, Marta Rizzi, Reinhard E. Voll, Andrea Cavalli, Eriberto Natali, Patrick Meier, Marc Stawiski, Johannes Mosbacher, Annette Mollet, Miriam Capri, Enrico Giampieri, Aurelia Santoro and Erik Schkommodau declare that they have no conflict of interest. Enkelejda Miho owns shares in aiNET GmbH. Ethics approval This study, involving human participants, complies with the Declaration of Helsinki and has received approvals from the appropriate medical ethical committees. The study has been approved by the CHU Strasbourg Medical Ethical Committee under the approval number CPP- IV- Est- 08/02/2011. Participants gave their informed consent prior to their involvement in the study., (© 2024. The Author(s).)
Published: 2024
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40. The cGAS-STING pathway in HIV-1 and Mycobacterium tuberculosis coinfection.

Author: Han X, Wang X, Han F, Yan H, Sun J, Zhang X, Moog C, Zhang C, and Su B
Abstract: Mycobacterium tuberculosis (M. tuberculosis) infection is the most common opportunistic infection in human immunodeficiency virus-1 (HIV-1)-infected individuals, and the mutual reinforcement of these two pathogens may accelerate disease progression and lead to rapid mortality. Therefore, HIV-1/M. tuberculosis coinfection is one of the major global public health concerns. HIV-1 infection is the greatest risk factor for M. tuberculosis infection and increases the likelihood of endogenous relapse and exogenous reinfection with M. tuberculosis. Moreover, M. tuberculosis further increases HIV-1 replication and the occurrence of chronic immune activation, accelerating the progression of HIV-1 disease. Exploring the pathogenesis of HIV-1/M. tuberculosis coinfections is essential for the development of novel treatments to reduce the global burden of tuberculosis. Innate immunity, which is the first line of host immune defense, plays a critical role in resisting HIV-1 and M. tuberculosis infections. The role of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, which is a major DNA-sensing innate immune signaling pathway, in HIV-1 infection and M. tuberculosis infection has been intensively studied. This paper reviews the role of the cGAS-STING signaling pathway in HIV-1 infection and M. tuberculosis infection and discusses the possible role of this pathway in HIV-1/M. tuberculosis coinfection to provide new insight into the pathogenesis of HIV-1/M. tuberculosis coinfection and the development of novel therapeutic strategies., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Published: 2024
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41. Early diagnosis of immunodeficient patients with partial albinism: The role of hair study and peripheral blood smear.

Author: Tajik S, Fazlollahi MR, Alizadeh Z, Badalzadeh M, Houshmand M, Razaghian A, Bahram S, Molitor A, Carapito R, Shariat M, Hamidieh AA, Behniafard N, Abdolkarimi B, Rostami T, Moin M, and Pourpak Z
Subjects: Humans, Male, Female, Child, Preschool, Child, Infant, Piebaldism diagnosis, Piebaldism genetics, Chediak-Higashi Syndrome diagnosis, Chediak-Higashi Syndrome genetics, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes immunology, Albinism, Oculocutaneous diagnosis, Albinism, Oculocutaneous genetics, Adolescent, Primary Immunodeficiency Diseases diagnosis, Primary Immunodeficiency Diseases genetics, Primary Immunodeficiency Diseases immunology, Genetic Testing methods, Hermanski-Pudlak Syndrome diagnosis, Hermanski-Pudlak Syndrome genetics, Mutation, Albinism diagnosis, Albinism genetics, Lymphohistiocytosis, Hemophagocytic, Hair immunology, Early Diagnosis
Abstract: Background: Primary immunodeficiency diseases (inborn errors of immunity) with partial albinism are a group of autosomal recessive syndromes including Chediak Higashi Syndrome (CHS), Griscelli Syndrome type 2 (GS2), Hermansky-Pudlak Syndromes type 2 and 10 (HPS2, HPS10), Vici syndrome and P14/LAMTOR2 deficiency., Methods: Twenty-five patients including 10 CHS, 10 GS2, and 5 HPS2 were evaluated in this study within the last 10 years. Five cases with oculocutaneous albinism (OCA) and 5 healthy subjects without albinism were used as two control groups. Genetic analyses were performed by whole exome or panel sequencing or targeted Sanger sequencing. Subsequently, leukocyte granules in peripheral blood smear and hair shaft were examined as screening tests., Results: Giant granules were only presented in the leukocytes cytoplasm of 10/10 CHS patients. The uneven cluster of pigments and giant melanin granules in hair samples were observed in 10/10 GS2 and 10/10 CHS patients, respectively. In both 5/5 OCA and 5/5 HPS2 patients, there were regular pigments in the middle of hair shafts. Genetic analyses were performed for all patients, revealing 7 novel variants in LYST gene for CHS patients and 4 novel variants in AP3B1 for HPS2 patients., Conclusion: Receiving hematopoietic stem cell transplantation (HSCT) in a timely manner is crucial in CHS and GS2 patients; therefore, screening tests may provide a vital clue for early diagnosis in these patients. However, the final confirmation of CHS, GS2, and HPS2 disorders is done by genetic assay., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Published: 2024
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42. Cryo-EM reveals structural basis for human AIM/CD5L recognition of polymeric immunoglobulin M.

Author: Chen Q, Ishii K, Mori H, Nishijima A, Arai S, Miyazaki T, and Rosenthal PB
Subjects: Humans, Apoptosis Regulatory Proteins metabolism, Apoptosis Regulatory Proteins chemistry, Cryoelectron Microscopy, Models, Molecular, Protein Domains, Receptors, Scavenger metabolism, Receptors, Scavenger chemistry, Immunoglobulin M immunology, Immunoglobulin M metabolism, Protein Binding
Abstract: Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM's C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs)., (© 2024. The Author(s).)
Published: 2024
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43. Targeting the MAtrix REgulating MOtif abolishes several hallmarks of cancer, triggering antitumor immunity.

Author: Li C, Kaur A, Pavlidaki A, Spenlé C, Rajnpreht I, Donnadieu E, Salomé N, Molitor A, Carapito R, Wack F, Erne W, Lefebvre O, Averous G, Mitrentsi I, Loustau T, and Orend G
Subjects: Humans, Animals, Mice, Female, Cell Line, Tumor, Breast Neoplasms immunology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Extracellular Matrix metabolism, Signal Transduction drug effects, Peptides pharmacology, Chemokine CXCL12 metabolism, Fibronectins metabolism, Tenascin metabolism, Tumor Microenvironment immunology, Tumor Microenvironment drug effects
Abstract: Tumor-targeted therapies have often been inefficient due to the lack of concomitant control over the tumor microenvironment. Using an immunocompetent autologous breast cancer model, we investigated a MAtrix REgulating MOtif (MAREMO)-mimicking peptide, which inhibits the protumorigenic extracellular matrix (ECM) molecule tenascin-C that activates several cancer hallmarks. In cultured cells, targeting the MAREMO blocks tenascin-C signaling involved in cell adhesion and immune-suppression by inhibiting tenascin-C interactions with fibronectin, TGFβ, CXCL12, and others, thereby blocking downstream events. Using RNASequencing and various genetic, molecular, in situ, and in vivo assays, we demonstrate that the MAREMO peptide similarly blocks multiple tenascin-C functions in vivo. This includes releasing tumor-infiltrating leukocytes, including CD8+ T cells, from the stroma. The MAREMO peptide also triggers interferon signaling, restoring antitumor immunity, contributing to tumor growth inhibition and reduced dissemination. The MAREMO peptide targets tumor cells directly by promoting growth suppression and inhibiting phenotypic plasticity, subsequently enhancing responsiveness to the endogenous death inducer tumor necrosis factor-related apoptosis-inducing ligand, as shown by a loss-of-function approach. Moreover, the MAREMO peptide largely subdues the tumor bed by depleting fibroblasts, repressing tenascin-C and other ECM molecules, and restoring the function of the few remaining blood vessels. In conclusion, targeting tenascin-C with a MAREMO peptide represents a powerful anticancer strategy with a broad inhibition of several cancer hallmarks., Competing Interests: Competing interests statement:The authors declare no competing interest.
Published: 2024
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44. Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France.

Author: Maanaoui M, Lenain R, Foucher Y, Buron F, Blancho G, Antoine C, Caillard S, Kessler L, Le Quintrec M, Villard O, Anglicheau D, Büchler M, Brodin-Sartorius A, Frimat L, Malvezzi P, Lablanche S, Badet L, Esposito L, Chetboun M, Hamroun A, Kerr-Conte J, Berney T, Vantyghem MC, Hazzan M, and Pattou F
Subjects: Humans, Male, Female, Retrospective Studies, France epidemiology, Adult, Middle Aged, Diabetes Mellitus, Type 1 surgery, Diabetes Mellitus, Type 1 therapy, Diabetes Mellitus, Type 1 complications, Kidney Transplantation, Islets of Langerhans Transplantation methods, Graft Survival
Abstract: Background: Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes., Methods: In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis., Findings: Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36)., Interpretation: In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide., Funding: Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté., Competing Interests: Declaration of interests MM, RL, YF, FB, GB, CA, LK, MLQ, DA, MB, AB-S, LF, PM, SL, LB, LE, MC, AH, JK-C, TB, M-CV, MH, and FP declare no competing interests. SC declares support for attending meetings or travel from Astra Zeneca, Alexion, Sanofi, and Pierre Fabre and participation on a data safety monitoring board or advisory board from Astra Zeneca, Alexion, Chiesi, Pierre Fabre, Pfizer, and Samsung Bioepis. OV declares payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Sanofi-Aventis, Eli-Lilly, and Novo-Nordisk and support for attending meetings or travel from Sanofi-Aventis., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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45. Unpredicted protective function of Fc-mediated inhibitory antibodies for HIV and SARS-CoV-2 vaccines.

Author: Lin LY, Gantner P, Li S, Su B, and Moog C
Abstract: Developing effective vaccines is necessary in combating new virus pandemics. For HIV and SARS-CoV-2, the induction of neutralizing antibodies (NAb) is important for vaccine protection; however, the exact mechanisms underlying protection require further study. Recent data emphasize that even Abs that do not exhibit neutralizing activity may contribute to immune defense. Abs exhibiting this function may counter virus mutations, which are acquired to escape from NAbs, and therefore, broaden the protective Ab response induced by vaccination. However, the steps leading to Ab Fc-mediated inhibition are complex. How can these functions be measured in vitro? What inhibitory assay is the most physiologically relevant at mimicking effective in vivo protection? This review provides a comprehensive update on the current knowledge gaps on the Ab Fc-mediated functions involved in HIV and SARS-CoV-2 protection. Understanding the inhibitory effects of these Abs is vital for designing the next generation of protective HIV and SARS-CoV-2 vaccines., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Published: 2024
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46. A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease.

Author: Molitor A, Lederle A, Radosavljevic M, Sapuru V, Zavorka Thomas ME, Yang J, Shirin M, Collin-Bund V, Jerabkova-Roda K, Miao Z, Bernard A, Rolli V, Grenot P, Castro CN, Rosenzwajg M, Lewis EG, Person R, Esperón-Moldes US, Kaare M, Nokelainen PT, Batzir NA, Hoffer GZ, Paul N, Stemmelen T, Naegely L, Hanauer A, Bibi-Triki S, Grün S, Jung S, Busnelli I, Tripolszki K, Al-Ali R, Ordonez N, Bauer P, Song E, Zajo K, Partida-Sanchez S, Robledo-Avila F, Kumanovics A, Louzoun Y, Hirschler A, Pichot A, Toker O, Mejía CAM, Parvaneh N, Knapp E, Hersh JH, Kenney H, Delmonte OM, Notarangelo LD, Goetz JG, Kahwash SB, Carapito C, Bajwa RPS, Thomas C, Ehl S, Isidor B, Carapito R, Abraham RS, Hite RK, Marcus N, Bertoli-Avella A, and Bahram S
Subjects: Humans, Male, Female, Calcium metabolism, Child, Mutation, Jurkat Cells, Child, Preschool, Genes, Dominant, Pedigree, Phenotype, Inositol 1,4,5-Trisphosphate Receptors genetics, Inositol 1,4,5-Trisphosphate Receptors metabolism
Abstract: Inositol 1,4,5-trisphosphate (IP3) receptor type 1 ( ITPR1 ), 2 ( ITPR2 ), and 3 ( ITPR3 ) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant-NM_002224.3:c.7570C>T, p.Arg2524Cys-causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium homeostasis, mitochondrial malfunction, CD4 + lymphopenia, a quasi-absence of naïve CD4 + and CD8 + cells, an increase in memory cells, and a distinct TCR repertoire. The calcium defect was recapitulated in Jurkat knock-in. Site-directed mutagenesis displayed the exquisite sensitivity of Arg 2524 to any amino acid change. Despite the fact that all patients had severe immunodeficiency, they also displayed variable multisystemic involvements, including ectodermal dysplasia, Charcot-Marie-Tooth disease, short stature, and bone marrow failure. In conclusion, unlike previously reported ITPR1-3 deficiencies leading to narrow, mainly neurological phenotypes, a recurrent dominant ITPR3 variant leads to a multisystemic disease, defining a unique role for IP3R3 in the tetrameric IP3R complex.
Published: 2024
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47. CAR-T cells for treating systemic lupus erythematosus: A promising emerging therapy.

Author: Guffroy A, Jacquel L, Guffroy B, and Martin T
Subjects: Humans, Receptors, Chimeric Antigen immunology, Female, Male, Treatment Outcome, Lupus Erythematosus, Systemic therapy, Lupus Erythematosus, Systemic immunology, Immunotherapy, Adoptive methods
Abstract: Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
Published: 2024
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48. Study of the feasibility of outpatient sacrocolpopexy by laparoscopy.

Author: Collin-Bund V, Viviani V, Meyer N, Goetsch T, Boisramé T, Faller E, Lecointre L, Gabriele V, Akladios C, Garbin O, and Host A
Subjects: Humans, Female, Middle Aged, Prospective Studies, Aged, Gynecologic Surgical Procedures methods, Patient Readmission statistics & numerical data, Laparoscopy methods, Feasibility Studies, Pelvic Organ Prolapse surgery, Quality of Life, Ambulatory Surgical Procedures methods
Abstract: Introduction: Laparoscopic sacrocolpopexy (LSCP) is currently the gold standard surgical technique for treating pelvic prolapse. This study aimed to evaluate the feasibility of laparoscopic sacrocolpopexy in ambulatory care., Patients and Methods: This prospective study was conducted to evaluate the feasibility of LSCP in women who visited the outpatient department of obstetrics and gynecology at the University Hospital of Strasbourg between July 2018 and December 2021. All women with indications for laparoscopic sacrocolpopexy for prolapse treatment who were willing to be treated as outpatients were included. The main criterion of the study was to evaluate the rate of re-hospitalization between discharge from the outpatient department after LSCP and postoperative follow-up consultations., Results: Among the whole population (57/200, 28.5 %) included, 4 (7 %) were hospitalized. The quality of life was not altered with a preserved EuroQol (EQ-5D) quality of life score with a mean score of 73±18.4 standard deviation (SD) 95 % confidence interval (CI) (67.9; 78.1) on postoperative day 3 (D3) and 91.2 ± 16.3 SD 95 % CI (86.2-96) on D30. On D1, D2, D3, and D7, the anxiety rate evaluated by State-Trait Anxiety Inventory score (STAI Y-A) remained low, with mean scores of 24.8 ± 9.6 SD 95 % [23.4-26.5] on D30. All patients were satisfied or very satisfied with the procedure and outpatient management, with an average score of 9.6/10 (range: 8-10)., Conclusion: This prospective, monocentric study evaluating the feasibility of outpatient LSCP reported demonstrated low rates of complications and re-hospitalization after outpatient management. Furthermore, the patients' quality of life was not altered, and they patients were satisfied with this type of management., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)
Published: 2024
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49. Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.

Author: Oda H, Manthiram K, Chavan PP, Rieser E, Veli Ö, Kaya Ö, Rauch C, Nakabo S, Kuehn HS, Swart M, Wang Y, Çelik NI, Molitor A, Ziaee V, Movahedi N, Shahrooei M, Parvaneh N, Alipour-Olyei N, Carapito R, Xu Q, Preite S, Beck DB, Chae JJ, Nehrebecky M, Ombrello AK, Hoffmann P, Romeo T, Deuitch NT, Matthíasardóttir B, Mullikin J, Komarow H, Stoddard J, Niemela J, Dobbs K, Sweeney CL, Anderton H, Lawlor KE, Yoshitomi H, Yang D, Boehm M, Davis J, Mudd P, Randazzo D, Tsai WL, Gadina M, Kaplan MJ, Toguchida J, Mayer CT, Rosenzweig SD, Notarangelo LD, Iwai K, Silke J, Schwartzberg PL, Boisson B, Casanova JL, Bahram S, Rao AP, Peltzer N, Walczak H, Lalaoui N, Aksentijevich I, and Kastner DL
Subjects: Humans, Female, Male, NF-kappa B metabolism, Ubiquitin-Protein Ligases genetics, Inflammation immunology, Inflammation genetics, B-Lymphocytes immunology, Loss of Function Mutation, Fibroblasts metabolism, Fibroblasts immunology, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Animals, Mice, Alleles, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes immunology, Nerve Tissue Proteins, Ubiquitins
Abstract: The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members. Both SHARPIN-deficient and HOIP-deficient individuals showed a substantial reduction of secondary lymphoid germinal center B cell development. Treatment of one SHARPIN-deficient individual with anti-TNF therapies led to complete clinical and transcriptomic resolution of autoinflammation. These findings underscore the critical function of the LUBAC as a gatekeeper for cell death-mediated immune dysregulation in humans., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
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50. Correction: An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Author: Guffroy A, Jacquel L, Seeleuthner Y, Paul N, Poindron V, Maurier F, Delannoy V, Voegeli AC, Zhang P, Nespola B, Molitor A, Apithy MJ, Soulas-Sprauel P, Martin T, Voll RE, Bahram S, Gies V, Casanova JL, Cobat A, Boisson B, Carapito R, and Korganow AS
Published: 2024
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