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1. Etoposide treatment in secondary hemophagocytic syndrome: impact on healthcare-associated infections and survival

Author: Thibault Dupont, Michael Darmon, Eric Mariotte, Virginie Lemiale, Jehane Fadlallah, Adrien Mirouse, Lara Zafrani, Elie Azoulay, and Sandrine Valade
Subjects: Hemophagocytic syndrome, Etoposide, Hospital acquired infections, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use. Results 168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI. Conclusions In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.
Published: 2022
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2. Leg‐type form of idiopathic multicentric Castleman disease associated with severe lower extremity chronic venous/lymphatic disease

Author: Thomas Ballul, Nabil Belfeki, Adèle deMasson, Véronique Meignin, Paul‐Louis Woerther, Antoine Martin, Elsa Poullot, Alain Wargnier, Jehane Fadlallah, Margaux Garzaro, Marion Malphettes, Claire Fieschi, Lucas Maisonobe, Hayat Bensekhri, Hélène Guillot, Rémi Bertinchamp, Marie Jachiet, Justine Poirot, Lionel Galicier, Eric Oksenhendler, and David Boutboul
Subjects: Castleman disease, chronic venous disease, lymphedema, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disease of unknown etiology. Deciphering mechanisms involved in CD pathogenesis may help improving patients’ care. Six cases of stereotyped sub‐diaphragmatic iMCD affecting lower limb‐draining areas and associated with severe and often ulcerative lower extremity chronic dermatological condition were identified in our cohort. Pathological examination revealed mixed or plasma‐cell type MCD. In three patients, shotgun metagenomics failed to identify any pathogen in involved lymph nodes. Antibiotics had a suspensive effect while rituximab and tocilizumab failed to improve the condition. This novel entity requires a specific approach and exclusion of potentially harmful immunomodulation.
Published: 2022
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3. Pre-COVID-19 Immunity to Common Cold Human Coronaviruses Induces a Recall-Type IgG Response to SARS-CoV-2 Antigens Without Cross-Neutralisation

Author: Makoto Miyara, Melissa Saichi, Delphine Sterlin, François Anna, Stéphane Marot, Alexis Mathian, Mo Atif, Paul Quentric, Audrey Mohr, Laetitia Claër, Christophe Parizot, Karim Dorgham, Hans Yssel, Jehane Fadlallah, Thibaut Chazal, Julien Haroche, Charles-Edouard Luyt, Julien Mayaux, Alexandra Beurton, Neila Benameur, David Boutolleau, Sonia Burrel, Sophia de Alba, Sasi Mudumba, Rick Hockett, Cary Gunn, Pierre Charneau, Vincent Calvez, Anne-Geneviève Marcelin, Alain Combes, Alexandre Demoule, Zahir Amoura, and Guy Gorochov
Subjects: COVID-19, humoral immune response, coronaviral infection, IgG, IgA, Immunologic diseases. Allergy, RC581-607
Abstract: The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.
Published: 2022
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4. Coagulation disorders in patients with severe hemophagocytic lymphohistiocytosis.

Author: Sandrine Valade, Bérangère S Joly, Agnès Veyradier, Jehane Fadlallah, Lara Zafrani, Virginie Lemiale, Amélie Launois, Alain Stepanian, Lionel Galicier, Claire Fieschi, Adrien Mirouse, Jean Jacques Tudesq, Anne-Claire Lepretre, Elie Azoulay, Michael Darmon, and Eric Mariotte
Subjects: Medicine, Science
Abstract: BackgroundCoagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH.MethodsWe prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) ResultsCoagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2∙65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p = 0∙021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], pConclusionsHyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.
Published: 2021
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5. Aplastic anemia related to thymoma: a survey on behalf of the French reference center of aplastic anemia and a review of the literature

Author: Nicolas Gendron, Flore Sicre de Fontbrune, Alice Guyard, Jehane Fadlallah, Sylvain Chantepie, Maud D’Aveni, Ronan Le Calloch, Alice Garnier, Marie-Anne Couturier, Véronique Morel, Claire Bernard, Louis Terriou, Estibaliz Lazaro, Gérard Socié, and Régis Peffault de Latour
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2020
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6. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus.

Author: Alexis Mathian, Romain Jouenne, Driss Chader, Fleur Cohen-Aubart, Julien Haroche, Jehane Fadlallah, Laetitia Claër, Lucile Musset, Guy Gorochov, Zahir Amoura, and Makoto Miyara
Subjects: Medicine, Science
Abstract: A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA- cells; and (3) non-suppressive FoxP3lowCD45RA- cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53-8.43) at day 0 to 2.80% (0.83-14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50-12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02-20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20-17.70) at day 0 to 4.74% (1.03-9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.
Published: 2015
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7. Intestinal Candida albicans overgrowth in IgA deficiency

Author: Alicia Moreno-Sabater, Delphine Sterlin, Lejla Imamovic, Fabienne Bon, Anne-Cecile Normand, Cecile Gonnin, Marianne Gazzano, Merieme Bensalah, Karim Dorgham, Elyes Ben Salah, Aniss Acherar, Christophe Parizot, Virginie Rigourd, Hervé Begue, Frederic Dalle, Claude Bachmeyer, Christophe Hennequin, Hans Yssel, Marion Malphettes, Claire Fieschi, Jehane Fadlallah, and Guy Gorochov
Subjects: Immunology, Immunology and Allergy
Published: 2023
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8. A neomorphic mutation in the interferon activation domain of IRF4 causes a dominant primary immunodeficiency

Author: Romane Thouenon, Loïc Chentout, Nidia Moreno-Corona, Lucie Poggi, Emilia Puig Lombardi, Benedicte Hoareau, Yohann Schmitt, Chantal Lagresle-Peyrou, Jacinta Bustamante, Isabelle André, Marina Cavazzana, Anne Durandy, Jean-Laurent Casanova, Lionel Galicier, Jehane Fadlallah, Alain Fischer, and Sven Kracker
Subjects: Immunology, Immunology and Allergy
Abstract: Here, we report on a heterozygous interferon regulatory factor 4 (IRF4) missense variant identified in three patients from a multigeneration family with hypogammaglobulinemia. Patients’ low blood plasmablast/plasma cell and naïve CD4 and CD8 T cell counts contrasted with high terminal effector CD4 and CD8 T cell counts. Expression of the mutant IRF4 protein in control lymphoblastoid B cell lines reduced the expression of BLIMP-1 and XBP1 (key transcription factors in plasma cell differentiation). In B cell lines, the mutant IRF4 protein as wildtype was found to bind to known IRF4 binding motifs. The mutant IRF4 failed to efficiently regulate the transcriptional activity of interferon-stimulated response elements (ISREs). Rapid immunoprecipitation mass spectrometry of endogenous proteins indicated that the mutant and wildtype IRF4 proteins differed with regard to their respective sets of binding partners. Our findings highlight a novel mechanism for autosomal-dominant primary immunodeficiency through altered protein binding by mutant IRF4 at ISRE, leading to defective plasma cell differentiation.
Published: 2023
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9. Leg‐type form of idiopathic multicentric Castleman disease associated with severe lower extremity chronic venous/lymphatic disease

Author: Thomas Ballul, Nabil Belfeki, Adèle Masson, Véronique Meignin, Paul‐Louis Woerther, Antoine Martin, Elsa Poullot, Alain Wargnier, Jehane Fadlallah, Margaux Garzaro, Marion Malphettes, Claire Fieschi, Lucas Maisonobe, Hayat Bensekhri, Hélène Guillot, Rémi Bertinchamp, Marie Jachiet, Justine Poirot, Lionel Galicier, Eric Oksenhendler, and David Boutboul
Abstract: Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disease of unknown etiology. Deciphering mechanisms involved in CD pathogenesis may help improving patients' care. Six cases of stereotyped sub-diaphragmatic iMCD affecting lower limb-draining areas and associated with severe and often ulcerative lower extremity chronic dermatological condition were identified in our cohort. Pathological examination revealed mixed or plasma-cell type MCD. In three patients, shotgun metagenomics failed to identify any pathogen in involved lymph nodes. Antibiotics had a suspensive effect while rituximab and tocilizumab failed to improve the condition. This novel entity requires a specific approach and exclusion of potentially harmful immunomodulation.
Published: 2021
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10. Post-traumatic stress disorder and quality of life alterations in survivors of immune-mediated thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome

Author: Elie Azoulay, Virginie Souppart, Nancy Kentish-Barnes, Ygal Benhamou, Bérangère S. Joly, Lara Zafrani, Adrien Joseph, Emmanuel Canet, Claire Presne, Maximilien Grall, Yoann Zerbib, François Provot, Jehane Fadlallah, Eric Mariotte, Tomas Urbina, Agnès Veyradier, and Paul Coppo
Subjects: Critical Care and Intensive Care Medicine
Published: 2023
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11. Campylobacter infection in 4 patients treated with ibrutinib

Author: Boris Sorin, Julien Vigneron, Jehane Fadlallah, Johanna Mondesir, Claire Fieschi, Eric Oksenhendler, Lionel Galicier, and Marion Malphettes
Subjects: Microbiology (medical), Diarrhea, Infectious Diseases, Pyrimidines, Piperidines, Adenine, Campylobacter Infections, Agammaglobulinaemia Tyrosine Kinase, Humans, Pyrazoles, General Medicine, Leukemia, Lymphocytic, Chronic, B-Cell, Protein Kinase Inhibitors
Abstract: Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B-cell lymphoproliferative disorders. Patients with genetic BTK deficiency are susceptible to recurrent and severe Campylobacter infections. We report 4 patients treated with ibrutinib who developed chronic or extra-digestive campylobacteriosis resembling ibrutinib-related adverse events including diarrhea (n = 4), panniculitis (n = 2), and arthritis (n = 1). Microbiological explorations identified Campylobacter jejuni (n = 3) or Campylobacter coli (n = 1). All the patients completely recovered after a short course of oral antibiotic therapy. In patients treated with ibrutinib presenting with chronic diarrhea, dermatological, or rheumatological manifestations, campylobacteriosis should be ruled out before attributing the symptoms to ibrutinib and discuss its discontinuation.
Published: 2022

12. Characteristics of thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly syndrome: a retrospective study from a large Western cohort

Author: Margaux Garzaro, David Boutboul, B. Dunogué, Rémi Bertinchamp, Lionel Galicier, Frédéric Vandergeynst, Mirlinda Berisha, Maximilien Grall, Virginie De Wilde, Noémie Saada, Eric Oksenhendler, Jehane Fadlallah, Laurence Gérard, Lucas Maisonobe, Stephanie Guillet, M. Hie, Marion Malphettes, Lara Zafrani, Claire Fieschi, Louise Damian, Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Henri Mondor, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Pediatrics, medicine.medical_specialty, Biopsy, Clinical Decision-Making, Anasarca, Organomegaly, anasarca, Diagnosis, Differential, chemistry.chemical_compound, Young Adult, tocilizumab, Tocilizumab, rituximab, Positron Emission Tomography Computed Tomography, Medicine, Humans, Retrospective Studies, fever, business.industry, urogenital system, Castleman Disease, Disease Management, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Syndrome, Middle Aged, Prognosis, Combined Modality Therapy, Immunohistochemistry, Phenotype, Treatment Outcome, chemistry, Reticulin fibrosis, idiopathic multicentric Castleman disease, Cohort, Inclusion and exclusion criteria, Western thrombocytopenia, Rituximab, Female, Disease Susceptibility, medicine.symptom, business, medicine.drug, reticulin fibrosis and organomegaly syndrome
Abstract: International audience; Idiopathic multicentric Castleman disease (iMCD) is a non-clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD-not otherwise specified (iMCD-NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD-NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD-NOS, respectively. The two-year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients.
Published: 2022
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13. A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients

Author: David Boutboul, Julien Calvani, Lionel Galicier, Cyrielle Robe, Margaux Garzaro, Jehane Fadlallah, Jean-Michel Cayuela, Laurence Gérard, Wendy Cuccuini, Elsa Poullot, Rémi Bertinchamp, Véronique Meignin, Philippe Gaulard, and Eric Oksenhendler
Subjects: Adult, Male, medicine.medical_specialty, CD58, HIV Infections, CD38, Gastroenterology, Pathology and Forensic Medicine, Interquartile range, hemic and lymphatic diseases, Internal medicine, Lymphoma, Primary Effusion, Biomarkers, Tumor, Medicine, Humans, CD20, biology, business.industry, Middle Aged, CD79A, medicine.disease, Immunohistochemistry, biology.protein, Surgery, Primary effusion lymphoma, Anatomy, CD5, business, CD8
Abstract: Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus-associated PELs, including 14 EBV+ and 5 EBV- PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV- cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV+ and EBV- PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P=0.62).
Published: 2021

14. Sinusoidal obstruction syndrome: a warning about autologous stem cell transplantation preceded by regimens containing oxaliplatin

Author: Frédérique Kuhnowski, Jean Philippe Richardet, Marie-Pierre Moles, Sébastien Mulé, Sylvie Glaisner, Manel Bedoui, Jehane Fadlallah, Julien Calderaro, Luc-Matthieu Fornecker, Pierre-Edouard Debureaux, Daniel Azoulay, Delphine Le Febvre de Nailly, Jerome Tamburini, Jehan Dupuis, Emmanuelle Tavernier, Corinne Haioun, David Sibon, and Vincent Camus
Subjects: Transplantation, medicine.medical_specialty, business.industry, Hematopoietic Stem Cell Transplantation, Hepatic Veno-Occlusive Disease, Hematology, Transplantation, Autologous, Oxaliplatin, Surgery, Autologous stem-cell transplantation, medicine, Humans, business, medicine.drug
Published: 2020
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15. Iron deficiency, an unusual cause of thrombocytopenia: results from a multicenter retrospective case-controlled study

Author: Marc Michel, Caroline Morbieu, Jehane Fadlallah, Valentine Lousteau, Orianne Wagner-Ballon, Luc Darnige, Tessa Huscenot, Marie Le Cann, Delphine Gobert, Nicolas Limal, Julien Rohmer, Alexis Mathian, Anne-Marie Ronchetti, and Laetitia Languille
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Possible diagnosis, Humans, Platelet, Diagnostic Errors, Aged, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic, Anemia, Iron-Deficiency, Thrombocytosis, Platelet Count, business.industry, Age Factors, Case-control study, Hematology, General Medicine, Iron deficiency, Middle Aged, medicine.disease, Thrombocytopenia, Immune thrombocytopenia, Iron-deficiency anemia, 030220 oncology & carcinogenesis, Female, business, Iron therapy, 030215 immunology
Abstract: Iron deficiency anemia (IDA) is often associated with mild to moderate thrombocytosis, and iron deficiency–associated thrombocytopenia (IDAT) is much more uncommon and often misdiagnosed as immune thrombocytopenia (ITP). To better describe the features of IDAT, we conducted a retrospective multicenter case-control study. We identified 10 patients (9 women) with a definite diagnosis IDAT, with a median age of 43.5 [range, 16–72] years and a median platelet count of 30.5 × 109/L [range, 21–80], and 7 patients with a possible diagnosis of IDAT. Bleeding manifestations were absent in all patients but one. All the patients recovered (platelet count ≥ 150 × 109/L) upon iron therapy ± red blood cell transfusion after a median time of 6 [4–39] days. When compared with 30 randomly newly diagnosed ITP patients matched on age, the baseline platelet count was significantly lower in ITP (median = 7 × 109/L [4–59], p
Published: 2019
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16. Evolution of Nutritional Status after Early Nutritional Management in COVID-19 Hospitalized Patients

Author: Pierre Bel Lassen, Jehane Fadlallah, Pauline Faucher, Alexis Mathian, Dorothée Bedock, Leila Soares, Julie Couffignal, Jean-Michel Oppert, Zahir Amoura, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 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)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Male, Pediatrics, Longitudinal study, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Logistic regression, Severity of Illness Index, law.invention, 0302 clinical medicine, law, Risk Factors, Oxygen therapy, SARS-Cov2, TX341-641, 030212 general & internal medicine, Longitudinal Studies, 2. Zero hunger, Aged, 80 and over, Nutrition and Dietetics, Nutritional status, Middle Aged, Intensive care unit, Patient Discharge, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Intensive Care Units, Female, Nutrition Therapy, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Nutritional Status, malnutrition, Article, 03 medical and health sciences, medicine, nutritional management, Humans, pneumonia, albumin, Aged, 030109 nutrition & dietetics, Nutrition. Foods and food supply, business.industry, SARS-CoV-2, Oxygen Inhalation Therapy, COVID-19, medicine.disease, Malnutrition, Logistic Models, Nutrition Assessment, Observational study, business, Food Science
Abstract: Background &amp, Aims: SARS-CoV2 infection is associated with an increased risk of malnutrition. Although there are numerous screening and nutritional management protocols for malnutrition, only few studies have reported nutritional evolution after COVID-19. The objectives of this study were to describe the evolution of nutritional parameters between admission and 30 days after hospital discharge, and to determine predictive factors of poor nutritional outcome after recovery in adult COVID-19 patients. Methods: In this observational longitudinal study, we report findings after discharge in 91 out of 114 patients initially admitted for COVID-19 who received early nutritional management. Nutritional status was defined using GLIM criteria and compared between admission and day 30 after discharge. Baseline predictors of nutritional status at day 30 were assessed using logistic regression. Results: Thirty days after discharge, 28.6% of patients hospitalized for COVID-19 were malnourished, compared to 42.3% at admission. Half of malnourished patients (53%) at admission recovered a normal nutritional status after discharge. Weight trajectories were heterogeneous and differed if patients had been transferred to an intensive care unit (ICU) during hospitalization (p = 0.025). High oxygen requirement during hospitalization (invasive ventilation p = 0.016 (OR 8.3 [1.6–61.2]) and/or oxygen therapy over 5 L/min p = 0.021 (OR 3.2 [1.2–8.9]) were strong predictors of malnutrition one month after discharge. Conclusions: With early nutritional management, most patients hospitalized for COVID-19 improved nutritional parameters after discharge. These findings emphasize the importance of nutritional care in COVID-19 patients hospitalized in medicine departments, especially in those transferred from ICU.
Published: 2021
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17. Autoimmune hypoglycemia expands the biological spectrum of HHV8(+) multicentric Castleman disease

Author: David Boutboul, Eric Oksenhendler, Claire Fieschi, Pierre Arnautou, Lionel Galicier, Jehane Fadlallah, Djaouida Bengoufa, Nicolas Blin, Soraya Fellahi, Corinne Vigouroux, Elias Barrak, Viviane Queyrel-Moranne, Martine Auclair, Laurence Gérard, Lucy Chaillous, Clara Bouché, Marion Malphettes, and Rémi Bertinchamp
Subjects: biology, business.industry, Castleman Disease, Autoantibody, nutritional and metabolic diseases, Hematology, Autoimmune hypoglycemia, Stimulus Report, Hypoglycemia, Insulin receptor, Insulin signal transduction pathway and regulation of blood glucose, Immunology, Herpesvirus 8, Human, biology.protein, Effective treatment, Medicine, Humans, Rituximab, Multicentric Castleman Disease, Complication, business, medicine.drug
Abstract: Key Points Autoimmune hypoglycemia belongs to the clinical spectrum of HHV8+ MCD and rituximab is an effective treatment of this condition. This rare complication is related to autoantibodies directed toward the insulin receptor and activating the insulin signaling pathway.
Published: 2021

18. Performance of diagnostic scores in thrombotic microangiopathy patients in the intensive care unit: a monocentric study

Author: Audrey De Jong, Virginie Lemiale, Etienne Ghrenassia, Bérangère S. Joly, Laure Calvet, Lionel Kerhuel, Michael Darmon, Alain Stepanian, Jehane Fadlallah, Lara Zafrani, Elie Azoulay, Sandrine Valade, Lionel Galicier, Eric Mariotte, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and MORNET, Dominique
Subjects: Adult, Erythrocyte Indices, Male, medicine.medical_specialty, Paris, Thrombotic microangiopathy, [SDV]Life Sciences [q-bio], Thrombotic thrombocytopenic purpura, 030204 cardiovascular system & hematology, Logistic regression, Risk Assessment, law.invention, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, law, Predictive Value of Tests, Risk Factors, hemic and lymphatic diseases, Internal medicine, medicine, Humans, International Normalized Ratio, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Receiver operating characteristic, business.industry, Platelet Count, Thrombotic Microangiopathies, Area under the curve, Reproducibility of Results, Hematology, Middle Aged, medicine.disease, Prognosis, Intensive care unit, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, 030220 oncology & carcinogenesis, Antibodies, Antinuclear, Creatinine, Cohort, Female, business, Biomarkers
Abstract: Early thrombotic thrombocytopenic purpura (TTP) recognition is critical as this disease is almost always lethal if not treated promptly with therapeutic plasma exchanges. Currently, as ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity is not widely available in emergency, scores have been developed to help differentiating TTP from other thrombotic microangiopathies (TMAs). The aim of this work was to study the accuracy of these diagnostic scores in the intensive care unit (ICU) setting. Performance of both Coppo and PLASMIC scores was studied in a cohort of adult TMA patients requiring admission to one university hospital ICU from 2006 to 2017. Receiver operating characteristic (ROC) curves were established, and confidence intervals of the area under the curve (AUC) were determined. Multivariate logistic regression analysis was performed to identify parameters specifically associated with TTP, to compare diagnostic scores and to elaborate more accurate diagnostic models. During the study period, 154 TMA patients required ICU admission, including 99 (64.2%) TTP and 55 (35.7%) non-TTP patients. AUC under the ROC curve in predicting TTP was 0.86 (95% confidence interval [CI]: 0.81–0.92) for the Coppo score, 0.67 (95% CI: 0.58–0.76) for the PLASMIC score, and 0.86 (95% CI: 0.81–0.92) for platelet count alone. Platelet count ≤20 G/L, determined as the best cut-off rate for thrombocytopenia, performed similarly to the Coppo score and better than the PLASMIC score to differentiate TTP from non-TTP patients, both using AUC ROC curve and logistic regression. In a monocentric cohort of TMA patients requiring ICU admission, the PLASMIC score had limited performance for the diagnosis of TTP. The performance of the Coppo score was good but similar to a single highly discriminant item: platelet count ≤20 G/L at admission.
Published: 2021
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19. Prevalence and severity of malnutrition in hospitalized COVID-19 patients

Author: Pauline Faucher, Zahir Amoura, C. Ciangura, Christine Poitou-Bernert, Jehane Fadlallah, Jean-Michel Oppert, Héléna Mosbah, Pierre Bel Lassen, Alexis Mathian, Pauline Moreau, Anne-Caroline Jeannin, Dorothée Bedock, Julie Couffignal, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut E3M [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Pediatrics, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Logistic regression, Severity of Illness Index, law.invention, 0302 clinical medicine, law, Nutritional knowledge, SARS-Cov2, Prevalence, Medicine, Hospital Mortality, Longitudinal Studies, 2. Zero hunger, Nutrition and Dietetics, Middle Aged, University hospital, Intensive care unit, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Female, Original Article, France, Coronavirus Infections, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, 030209 endocrinology & metabolism, 03 medical and health sciences, Betacoronavirus, Disease severity, Humans, In patient, Pandemics, Aged, 030109 nutrition & dietetics, business.industry, SARS-CoV-2, Albumin, Malnutrition, COVID-19, Pneumonia, medicine.disease, Nutrition Assessment, business
Abstract: International audience; Background & aims: Nutritional knowledge in patients with SARS-Cov2 infection (COVID-19) is limited. Our objectives were: i) to assess malnutrition in hospitalized COVID-19 patients, ii) to investigate the links between malnutrition and disease severity at admission, iii) to study the impact of malnutrition on clinical outcomes such as transfer to an intensive care unit (ICU) or death.Methods: Consecutive patients hospitalized in a medicine ward at a university hospital were included from March 21st to April 24th 2020 (n = 114, 60.5% males, age: 59.9 ± 15.9 years). Nutritional status was defined using Global Leadership Initiative on Malnutrition (GLIM) criteria. Clinical, radiological and biological characteristics of COVID-19 patients were compared according to the presence of malnutrition. Logistic regression was used to assess associations between nutritional parameters and unfavourable outcomes such as transfer to intensive care unit (ICU) or death.Results: The overall prevalence of malnutrition was 42.1% (moderate: 23.7%, severe: 18.4%). The prevalence of malnutrition reached 66.7% in patients admitted from ICU. No significant association was found between nutritional status and clinical signs of COVID-19. Lower albumin levels were associated with a higher risk of transfer to ICU (for 10 g/l of albumin, OR [95%CI]: 0.31 [0.1; 0.7]; p < 0.01) and this association was independent of age and CRP levels.Conclusions: COVID-19 in medical units dedicated to non-intensive care is associated with a high prevalence of malnutrition, especially for patients transferred from ICU. These data emphasize the importance of early nutritional screening in these patients to adapt management accordingly.
Published: 2020
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20. IgA dominates the early neutralizing antibody response to SARS-CoV-2

Author: Pierre Charneau, Jean Marc Lacorte, Laetitia Claër, Olivier Schwartz, Amélie Guihot, Cary Gunn, Rick Hockett, Pascale Ghillani, Hans Yssel, Alexis Mathian, Jehane Fadlallah, Timothée Bruel, Karim Dorgham, Paul Quentric, François Anna, Makoto Miyara, Salma Fourati, Charles Edouard Luyt, Guy Gorochov, Delphine Sterlin, Hervé Devilliers, Sasi Mudumba, Alexandra Beurton, Julien Mayaux, Zahir Amoura, Christophe Parizot, Audrey Mohr, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], 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), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-TheraVectys, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Saliva, Time Factors, viruses, Antibodies, Viral, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Humans, Medicine, Longitudinal Studies, Neutralizing antibody, Research Articles, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, SARS-CoV-2, business.industry, Case-control study, COVID-19, General Medicine, Antibodies, Neutralizing, Primary and secondary antibodies, STM r-articles, Immunity, Humoral, Immunoglobulin A, 3. Good health, Coronavirus, Immunoglobulin M, Case-Control Studies, Immunoglobulin G, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Antibody, business, Bronchoalveolar Lavage Fluid, Biomarkers, Research Article
Abstract: Early specific antibody responses against SARS-CoV-2 include IgG, IgM, and IgA, but IgA may neutralize virus and control infection to a larger extent., Early action of IgA Humoral immune responses play a critical role in protecting individuals against SARS-CoV-2 infection, particularly through the activity of neutralizing antibodies. Sterlin et al. measured humoral immune responses in the serum, saliva, and bronchoalveolar lavage fluid of SARS-CoV-2–infected patients who experienced a range of COVID-19 disease severity. IgA antibodies dominated the early SARS-CoV-2–specific antibody response compared with IgG and IgM concentrations in these fluids and was associated with expansion of IgA plasmablasts with mucosal homing characteristics. IgA serum concentrations peaked 3 weeks after symptom onset but persisted for several more weeks in saliva, and serum IgA was more potent than IgG in neutralizing SARS-CoV-2. These findings highlight the potential role of IgA during early SARS-CoV-2 infection., Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2–specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2–specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
Published: 2020
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21. IgA dominates the early neutralizing antibody response to SARS-CoV-2

Author: Cary Gunn, Rick Hockett, Salma Fourati, Jean-Marc Lacorte, Makoto Miyara, Pierre Charneau, Karim Dorgham, François Anna, Laetitia Claër, Amélie Guihot, Charles-Edouard Luyt, Pascale Ghillani, Jehane Fadlallah, Paul Quentric, Julien Mayaux, Delphine Sterlin, Christophe Parizot, Guy Gorochov, Zahir Amoura, Alexandra Beurton, Audrey Mohr, Hans Yssel, Alexis Mathian, and Sasi Mudumba
Subjects: Coronavirus disease 2019 (COVID-19), biology, Igm antibody, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunoglobulin E, Isotype, Antibody response, Immunology, biology.protein, Medicine, Antibody, business, Neutralizing antibody
Abstract: A major dogma in immunology has it that the IgM antibody response precedes secondary memory responses built on the production of IgG, IgA and, occasionaly, IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of specific, neutralizing, antibodies in serum and broncho-alveolar fluid of 145 patients with COVID-19. Surprisingly, early SARS-CoV-2-specific humoral responses were found to be typically dominated by antibodies of the IgA isotype. Peripheral expansion of IgA-plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. While the specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization, as compared to IgG. However, specific IgA serum levels notably decrease after one month of evolution. These results represent a challenging observation given the present uncertainty as to which kind of humoral response would optimally protect against re-infection, and whether vaccine regimens should consider boosting a potent, although, at least in blood, fading IgA response.One sentence SummaryWhile early specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization.
Published: 2020
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22. Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome with Bilateral Adrenal Hemorrhage in Two Caucasian Patients

Author: Grégoire Ducoux, Bouchra Asli, Arnaud Hot, Arthur Guerber, Jehane Fadlallah, and Cécile-Audrey Durel
Subjects: Male, medicine.medical_specialty, Abdominal pain, Adrenal Gland Diseases, Hemorrhage, 030204 cardiovascular system & hematology, Giant Lymph Node Hyperplasia, Anasarca, Gastroenterology, Organomegaly, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Fatal Outcome, 0302 clinical medicine, Tocilizumab, Internal medicine, medicine, Adrenal insufficiency, Humans, Edema, Renal Insufficiency, Myelofibrosis, Past medical history, business.industry, Castleman Disease, Articles, General Medicine, medicine.disease, Thrombocytopenia, chemistry, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, Adrenal Hemorrhage, Adrenal Insufficiency
Abstract: Case series Patients: Male, 19-year-old • Female, 31-year-old Final Diagnosis: TAFRO syndrome Symptoms: Fever • splenomegaly • lymphadenopathies Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of idiopathic multicentric Castleman disease. Adrenal hemorrhage has rarely been reported in TAFRO syndrome, and previous cases have mainly been Asian patients. This report is of two Caucasian patients with TAFRO syndrome presenting with acute adrenal insufficiency due to bilateral adrenal hemorrhage. Case Reports: Case 1 was a 19-year-old Caucasian man with no significant past medical history who was admitted with acute abdominal pain, vomiting, anorexia, and moderate weight loss. Case 2 was a 31-year-old Caucasian woman with no past medical history who was admitted to hospital with fever, dyspnea, thoracic and abdominal pain, polyarthralgia, and hypotension. Both patients had splenomegaly, mild lymphadenopathy, thrombocytopenia, acute kidney injury, and myelofibrosis. In both cases, lymph node biopsy histology showed mixed-type idiopathic multicentric Castleman disease. In both patients, a diagnosis of TAFRO was made, and they developed bilateral adrenal hemorrhage with adrenal insufficiency. Case 1 was treated with high-dose steroids, followed by tocilizumab infusion. Due to persistent thrombocytopenia, second-line treatment commenced with rituximab, but the patient relapsed two months later. Tocilizumab treatment was recommenced, which was followed by an immuno-allergic adverse event. He then had a good response to sirolimus. Case 2 died nine months after diagnosis due to acute respiratory distress. Conclusions: Two cases of TAFRO syndrome presented with acute adrenal insufficiency due to bilateral adrenal hemorrhage. The symptoms were only partially controlled with tocilizumab, rituximab, and tacrolimus. Adrenal hemorrhage may be a specific manifestation of TAFRO syndrome.
Published: 2020
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23. Human IgA binds a diverse array of commensal bacteria

Author: Martin R. Larsen, Asok Rajkumar, Carmen Capito, Hela El-Kafsi, Hans Yssel, Guy Gorochov, Delphine Sterlin, Olivia Joan Adams, Catherine Juste, Thomas Candela, Jean-Luc Charuel, Christophe Parizot, Karim Dorgham, Friederike Jönsson, Hedda Wardemann, Hélène Brisson, Stephan von Gunten, Richard D. Cummings, Gaëlle Autaa, Claire Fieschi, Alexandra Aubry, Christophe Trésallet, Jehane Fadlallah, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], University of Bern, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Université Paris Diderot - Paris 7 (UPD7), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, AgroParisTech, Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Harvard Medical School [Boston] (HMS), The study was financed by Inserm, and by Agence Nationale de la Recherche (MetAntibody, ANR-14-CE14-0013) to ML. Research in the laboratory of S. von Gunten is supported by the Swiss National Science Foundation (SNSF) grants 310030_184757 and 310030_162552, and by the Swiss Cancer League/Swiss Cancer Research (grant KFS-3941-08-2016)., ANR-14-CE14-0013,METAntibody,Spécificité des IgA sécrétoires et leur impact sur la composition du microbiote intestinal et sur l'immunité de l'hôte(2014), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Université Paris Diderot - Paris 7 (UPD7), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), Centre d'Immunologie et des Maladies Infectieuses (CIMI), 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), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunoglobulin A, Glycan, Immunology, 610 Medicine & health, digestive system, Technical Advances and Resources, Microbiology, Affinity maturation, 03 medical and health sciences, 0302 clinical medicine, fluids and secretions, stomatognathic system, Immunology and Allergy, Secretion, Microbiome, 030304 developmental biology, 0303 health sciences, biology, Mucosal Immunology, Isotype, 3. Good health, Polyclonal antibodies, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody
Abstract: Intestinal IgA is a key player in host-commensal symbiosis. Sterlin et al. report that human IgAs are microbiota cross-reactive at the clonal level. IgA1 and IgA2 mostly converge toward common gut microbiota targets but possess distinct carbohydrate repertoires., In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1−IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.
Published: 2020
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24. Correction: Human IgA bind a diverse array of commensal bacteria

Author: Alexandra Aubry, Olivia Joan Adams, Hela El-Kafsi, Delphine Sterlin, Martin R. Larsen, Christophe Trésallet, Thomas Candela, Jehane Fadlallah, Claire Fieschi, Stephan von Gunten, Christophe Parizot, Friederike Jönsson, Hans Yssel, Catherine Juste, Jean-Luc Charuel, Hedda Wardemann, Carmen Capito, Guy Gorochov, Asok Rajkumar, Hélène Brisson, Karim Dorgham, Gaëlle Autaa, Richard D. Cummings, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Immunoglobulin A, Immunology, biology.protein, Correction, Immunology and Allergy, 610 Medicine & health, Biology, Binding (Molecular Function), Commensalism, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology
Abstract: In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1-IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.
Published: 2020
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25. Un réservoir de lymphocytes B mémoires ayant résisté au rituximab participe aux rechutes à distance du traitement au cours de la thrombopénie immunologique de l’adulte

Author: Etienne Crickx, Matthieu Mahevas, J.C. Weill, A. Vandenberghe, Marc Michel, Imane Azzaoui, Pascal Chappert, Sandra K. Weller, C.A. Reynaud, Véronique Meignin, Bertrand Godeau, Aurélien Sokal, Tatiana Fadeev, Etienne Rivière, Sébastien Storck, R. Geoffrey, G. Bonnard, and Jehane Fadlallah
Subjects: Gastroenterology, Internal Medicine
Abstract: Introduction La thrombopenie immunologique de l’adulte (PTI) est une maladie autoimmune principalement mediee par des anticorps diriges contre les glycoproteines plaquettaires, dont la GPIIbIIIa. Au cours du PTI, une proportion de patients ayant repondu au rituximab (RTX) rechutent lors de la reconstitution lymphocytaire B. L’acces aux tissus spleniques de ces patients au moment precis de la rechute permet d’etudier la mise en place d’une nouvelle reponse auto-immune. L’objectif de ce travail etait de preciser si les cellules ayant initie la rechute etaient des lymphocytes B nouvellement generes par la moelle osseuse, ou des lymphocytes B memoires autoreactifs ayant resiste au rituximab. Patients et methodes Pour repondre a cette question, nous avons etudie les tissus spleniques de patients ayant repondu au rituximab puis rechute lors de la reconstitution lymphocytaire B. Nous avons combine l’identification en cellule unique de lymphocytes B anti-GpIIbIIa apres culture et differenciation, avec un sequencage haut debit des genes des chaines lourdes d’immunoglobulines (VH) des differentes sous populations B spleniques. Resultats Nous avons analyse les tissus spleniques de 8 patients, splenectomises pour une rechute 8 a 14 mois apres la derniere injection de RTX. L’etude histologique et par cytometrie en flux a montre que la reconstitution lymphocytaire B etait en cours, en parallele d’une reponse autoimmune faisant intervenir les centres germinatifs. L’analyse du profil mutationnel des segments VH par sequencage haut debit dans les differentes sous populations montrait une distribution bimodale, permettant de distinguer les lymphocytes B nouvellement generes (peu mutes) des lymphocytes B ayant resiste au RTX (tres mutes). L’etude de la specificite en cellule unique a revele la presence de cellules anti-GPIIbIIIa chez 5 patients, a la fois dans les populations des centres germinatifs (mediane 19 % [14–35]) et des lymphocytes B memoires (mediane 16 % [12–26]). En etudiant les relations clonales entre lymphocytes B du centre germinatif, lymphocytes B memoires, et plasmocytes, nous avons observe que des lymphocytes B memoires spleniques anti-GPIIbIIIa ayant resiste au RTX pouvaient retourner dans les centres germinatifs et/ou generer des plasmocytes autoreactifs, contribuant ainsi aux rechutes a distance du traitement. Conclusion En conclusion, nos donnees permettent de mieux comprendre les rechutes apres RTX et d’envisager de nouvelles strategies therapeutiques pour ameliorer les remissions a long terme dans le PTI, ainsi que dans d’autres pathologies autoimmunes mediees par les anticorps.
Published: 2020
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26. Les Immunoglobulines A dominent la réponse anticorps neutralisante précoce anti-SARS-CoV-2

Author: Pierre Charneau, Olivier Schwartz, Zahir Amoura, François Anna, Delphine Sterlin, Alexis Mathian, Guy Gorochov, Hervé Devilliers, Makoto Miyara, Audrey Mohr, Paul Quentric, Karim Dorgham, Christophe Parizot, Jehane Fadlallah, and Timothée Bruel
Subjects: Gastroenterology, Internal Medicine
Abstract: Introduction Un dogme en immunologie stipule que la reponse anticorps IgM precede les reponses IgG et IgA. Le nouveau coronavirus SARS-CoV-2 (syndrome respiratoire aigu severe coronavirus 2), agent pathogene a l’origine de la maladie a coronavirus 19 (COVID-19), induit une reponse anticorps specifique IgG, IgM et IgA. Les IgA anti-SARS-CoV-2 ont cependant ete peu etudiees jusqu’a present. Dans ce travail nous avons mesure les reponses humorales systemiques et muqueuses anti-SARS-CoV-2 en etudiant les isotypes IgG, IgA et IgM. Patients et methodes 135 patients adultes consecutifs atteints de COVID-19 ont ete inclus dans l’etude entre le 22 mars et le 24 avril 2020 et compares a 20 donneurs sains. Le phenotypage des lymphocytes B a ete realise en cytometrie en flux sur des cellules mononucleees du sang peripherique a partir d’echantillons sanguins de 38 patients. 214 echantillons de serum ont ete preleves chez 132 patients. Pour evaluer l’immunite locale, des lavages broncho-alveolaires et des echantillons salivaires ont ete collectes aupres, respectivement, de 10 patients hospitalises en reanimation et de 10 malades vus en consultation 1 a 2 mois apres leur guerison. Les anticorps IgA, IgM et IgG specifiques du SARS-CoV-2 ont ete mesures avec un panel de serologie multi-antigene Maverick ™ SARS-CoV-2. Des tests de neutralisation ont ete realises avec un pseudo-virus a partir des serums de 12 malades. Resultats Une expansion peripherique de plasmoblastes, en majorite secreteurs d’IgA, etait presente peu de temps apres le debut des symptomes et atteignait un pic au cours de la troisieme semaine. Environ 40 % des plasmoblastes exprimaient le recepteur de chimiokine CCR10, suggerant que ces derniers avaient un tropisme pulmonaire important. Cette premiere vague etait suivie d’une deuxieme vague de plasmoblastes secreteurs d’IgG qui devenait dominante 22 jours apres l’apparition des symptomes. Les IgG et IgA anti-RBD etaient detectees dans 7 et 15 des 48 echantillons seriques, respectivement, au cours de la premiere semaine (serum positifs: 31 % IgA vs 15 % IgG, p = 0,052). Les IgM anti-RBD n’etaient detectees que dans 7 de ces 48 echantillons. Le delai d’apparition des Ig anti-RBD etait significativement plus court pour les IgA que pour les IgG (p 92 % au cours de la 4e semaine apres l’apparition des symptomes. La frequence des patients avec des IgA anti-RBD culminait a 80 % autour du 22e jour puis diminuait a 23 % apres le 28e jour. La reponse IgA precoce anti-SARS-CoV-2 n’etait pas associee a la gravite clinique. Les preparations d’IgA purifiees neutralisaient plus le SARS-CoV-2 que les preparations d’IgG purifees. Le pouvoir de neutralisation du serum etait correle aux titres en IgA seriques anti-RBD, et non a ceux des IgG seriques anti-RBD. Huit echantillons salivaires sur 10 neutralisaient le SARS-CoV-2. Le pouvoir de neutralisation de la salive etait aussi correle aux titres d’IgA salivaire anti-RBD. Les IgA anti-RBD etaient plus abondantes dans la salive que dans le serum, ce qui suggere que les IgA anti-SARS-CoV-2 persistaient plus longtemps au niveau muqueux que dans le sang. Conclusion Nos resultats montrent que la reponse humorale precoce specifique anti-SARS-CoV-2 est dominee par les IgA qui ont un role cle dans la neutralisation du virus. La reponse IgA systemique semble cependant de courte duree, alors que la reponse IgA muqueuse persiste. Ces resultats apportent des informations importantes sur le type de reponse humorale qui protegerait de maniere optimale contre l’infection.
Published: 2020
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27. Aplastic anemia related to thymoma: a survey on behalf of the French reference center of aplastic anemia and a review of the literature

Author: Jehane Fadlallah, Nicolas Gendron, Estibaliz Lazaro, Alice Garnier, Marie-Anne Couturier, Alice Guyard, Régis Peffault de Latour, Sylvain Chantepie, Ronan Le Calloch, Louis Terriou, Véronique Morel, Maud d'Aveni, Gérard Socié, Claire Bernard, Flore Sicre de Fontbrune, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Département d'Anatomo-Pathologie [Hôpital Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut d'Hématologie de Basse-Normandie (IHBN), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier de Cornouaille, Centre hospitalier universitaire de Nantes (CHU Nantes), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et maladies infectieuses [Bordeaux], and CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André
Subjects: Pediatrics, medicine.medical_specialty, Thymoma, Anemia, business.industry, Anemia, Aplastic, Hematology, Thymus Neoplasms, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Surveys and Questionnaires, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Center (algebra and category theory), Aplastic anemia, business, Online Only Articles, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience
Published: 2019
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28. Long-term clinical outcome and HAVCR2 mutations in 70 patients with subcutaneous panniculitis-like T-cell lymphoma: a study from the French Cutaneous Lymphoma Group

Author: M. Bagot, Stéphane Barete, François Skowron, Pauline Brice, Gwenaël Hervé, David Michonneau, Béatrice Vergier, A. Finon, Caroline Ram-Wolff, Marie Beylot-Barry, A. Març Ais, Stéphane Dalle, Serge Boulinguez, F. Brunet-Possenti, Vanessa Szablewski, S. Laurent-Roussel, Eve Maubec, O. Carpentier, F. Sepulveda Garrido, G. Sonigo, E. Birckel, Olivier Dereure, V. Costes Martineau, Henri Adamski, R. Kerdraon, A. de Masson, I. Brocheriou, S. Oro, Agnès Carlotti, Fabien Guérin, F. Franck, O. Augereau, C. Bléchet, N. Bonnet, P. Moguelet, Jd. Bouaziz, Olivia Boccara, Gérard Socié, R. Dubois, F. Le Gall, F. Suarez, Marisa Battistella, L. Deschamps, Nicolas Ortonne, Nicolas Franck, B. Balme, G. Bens, G. de Saint-Basile, F. Comoz, D. Haidar, S. Taix, Sylvie Fraitag, Christine Bodemer, Jehane Fadlallah, E. Tournier, A. Mahe, Laurence Lamant, Guy Leverger, G. Bohelay, Michel D'Incan, S. Faiz, I. Beschet, Liliane Laroche, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Cognitives (ISC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Nord [CHU - APHM], CRLCC Henri Becquerel, CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de Dermatologie, Hôpital Bichat, AP-HP, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Pontificia Universidad Católica de Chile (UC), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre Hospitalier Régional d'Orléans (CHR), Laboratoire Hippolyte Fizeau (FIZEAU), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Service d’Anatomie et cytologie pathologiques [CHU Tenon], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Laboratoire d'aérologie (LA), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Dermatologie [Rennes] = Dermatology [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire d'aérologie (LAERO), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), CHU Trousseau [APHP], Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, medicine.medical_specialty, business.industry, HAVCR2, medicine.disease, Dermatology, Cutaneous lymphoma, 3. Good health, Oncology, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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29. Bortezomib and dexamethasone, an original approach for treating multi‐refractory warm autoimmune haemolytic anaemia

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

Author: Delphine Sterlin, Martin Larsen, Claire Fieschi, Guy Gorochov, Marion Malphettes, Jehane Fadlallah, Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and LARSEN, Martin
Subjects: 0301 basic medicine, Microbiology (medical), Immunoglobulin A, IgM, [SDV.IMM] Life Sciences [q-bio]/Immunology, microbiome, Gut flora, Cohort size, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Microbial ecology, Humans, IgA deficiency, Microbiome, Bacteria, biology, gut microbiota, CVID, Gastroenterology, Biodiversity, biology.organism_classification, Addendum, Gastrointestinal Microbiome, Common Variable Immunodeficiency, 030104 developmental biology, Infectious Diseases, Immunoglobulin M, Metagenomics, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology
Abstract: International audience; In a recently published article we report the metagenomic analysis of human gut microbiomes evolved in the absence of immunoglobulin A (IgA). We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. While our studyunderlines a rather expected pathobiont expansion, we at the same time highlight a less expected depletion in some typically beneficial symbionts. We also show that IgM partially supply IgA deficiency, explaining the relatively mild clinical phenotype associated with the early steps of thiscondition. Microbiome studies in patients should consider potential issues such as cohort size, human genetic polymorphism and treatments. In this commentary, we discuss how such issues were taken into account in our own study
Published: 2019
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31. The antibody/microbiota interface in health and disease

Author: Emma Slack, Delphine Sterlin, Guy Gorochov, Jehane Fadlallah, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], 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), Recherche clinique appliquée à l'hématologie ((EA_3518)), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), D.S. was supported for this work by a Pasteur/APHP interface fellowship, We thank members of the Gorochov and Slack labs for discussions and H. Yssel for critical reading of the paper., CHU Pitié-Salpêtrière [APHP], Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Immunoglobulin A, Immunology, Disease, Biology, Gut flora, digestive system, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Immunology and Allergy, Animals, Homeostasis, Humans, Intestinal Mucosa, Symbiosis, Immunity, Mucosal, Host Microbial Interactions, Compartmentalization (psychology), biology.organism_classification, 3. Good health, Gastrointestinal Microbiome, 030104 developmental biology, Immunoglobulin A, Secretory, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Function (biology), 030215 immunology
Abstract: International audience; The human intestine is densely colonized with commensal microbes that stimulate the immune system. While secretory Immunoglobulin (Ig) A is known to play a crucial role in gut microbiota compartmentalization, secretory IgM, and systemic IgG have recently been highlighted in host-microbiota interactions as well. In this review, we discuss important aspects of secretory IgA biology, but rather than focusing on mechanistic aspects of IgA impact on microbiota, we stress the current knowledge of systemic antibody responses to whole gut microbiota, in particular their generation, specificities, and function. We also provide a comprehensive picture of secretory IgM biology. Finally, therapeutic and diagnostic implications of these novel findings for the treatment of various diseases are outlined.
Published: 2019
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32. Treatment and outcome of Unicentric Castleman Disease: a retrospective analysis of 71 cases

Author: Pierre Mordant, Véronique Meignin, Lionel Galicier, Claire Fieschi, Sylvain Chawki, Jehane Fadlallah, David Boutboul, Antoine Dossier, Eric Oksenhendler, Laurence Gérard, and Marion Malphettes
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Asymptomatic, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Retrospective analysis, Medicine, Humans, Benign Lymphoproliferative Disorder, Retrospective Studies, Response rate (survey), business.industry, Castleman disease, Castleman Disease, Gold standard, Hematology, Middle Aged, medicine.disease, Surgery, Radiation therapy, Survival Rate, Regimen, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, 030215 immunology
Abstract: We retrospectively analysed 71 cases of Unicentric Castleman disease, a rare, usually asymptomatic, benign lymphoproliferative disorder presenting as a unique nodal mass. Although surgery is considered as the gold standard therapy, only 38 patients (54%) underwent initial surgical resection and 95% were cured. An additional 9 patients had surgery after an attempt at medical reduction. Reduction therapy was used in 21 patients with a 55% response rate, but without evidence for an optimal regimen. Radiotherapy was limited to 8 patients because of associated toxicity. Watch and wait was considered in 13 asymptomatic patients and 11 of these remained stable for up to 17 years.
Published: 2019

33. Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

Author: Pascale Ghillani-Dalbin, Lionel Galicier, Claire Fieschi, Hela El Kafsi, Martin Larsen, Karim Dorgham, Patricia Lepage, Jehane Fadlallah, David Boutboul, Makoto Miyara, Christophe Parizot, Guy Gorochov, Christophe Tresallet, Gaëlle Autaa, Marion Malphettes, Hans Yssel, Alexis Mathian, Sébastien André, Karine Clément, Catherine Juste, Zahir Amoura, Delphine Sterlin, Eric Oksenhendler, Florian Marquet, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Service d'immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7), CHU Saint Louis [APHP], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut National de la Recherche Agronomique (INRA), Service de nutrition [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [APHP], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], 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 Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: 0301 basic medicine, Immunology, Inflammation, Gut microbiota, Gut flora, Selective IgA deficiency, Systemic inflammation, anticommensal IgG, 03 medical and health sciences, Feces, 0302 clinical medicine, Western blot, intravenous immunoglobulin, medicine, Immunology and Allergy, Humans, biology, medicine.diagnostic_test, Common variable immunodeficiency, common variable immunodeficiency, biology.organism_classification, medicine.disease, Antibodies, Bacterial, 3. Good health, Gastrointestinal Microbiome, 030104 developmental biology, secretory IgA, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, Immunoglobulin G, Immunoglobulin A, Secretory, biology.protein, IgA deficiency, medicine.symptom, Antibody
Abstract: International audience; BACKGROUND: Commensals induce local IgA responses essential to the induction of tolerance to gut microbiota, but it remains unclear whether antimicrobiota responses remain confined to the gut.OBJECTIVE: The aim of this study was to investigate systemic and intestinal responses against the whole microbiota under homeostatic conditions and in the absence of IgA.METHODS: We analyzed blood and feces from healthy donors, patients with selective IgA deficiency (SIgAd), and patients with common variable immunodeficiency (CVID). Immunoglobulin-coated bacterial repertoires were analyzed by using combined bacterial fluorescence-activated cell sorting and 16S rRNA sequencing. Bacterial lysates were probed by using Western blot analysis with healthy donor sera.RESULTS: Although absent from the healthy gut, serum antimicrobiota IgG are present in healthy subjects and increased in patients with SIgAd. IgG converges with nonoverlapping secretory IgA specificities to target the same bacteria. Each individual subject targets a diverse microbiota repertoire with a proportion that correlates inversely with systemic inflammation. Finally, intravenous immunoglobulin preparations target CVID gut microbiota much less efficiently than healthy microbiota.CONCLUSION: Secretory IgA and systemic IgG converge to target gut microbiota at the cellular level. SIgAd-associated inflammation is inversely correlated with systemic anticommensal IgG responses, which might serve as a second line of defense. We speculate that patients with SIgAd could benefit from oral IgA supplementation. Our data also suggest that intravenous immunoglobulin preparations can be supplemented with IgG from IgA-deficient patient pools to offer better protection against gut bacterial translocations in patients with CVID.
Published: 2019
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34. Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis

Author: Catherine Juste, Catherine Lubetzki, Marina Vignes, Gaëlle Autaa, Romain Deschamps, Jennifer Aboab, Caroline Papeix, Christophe Parizot, Patricia Lepage, Karim Dorgham, Jehane Fadlallah, Savine Vicart, Guy Gorochov, Delphine Sterlin, Martin Larsen, Olivier Gout, Elisabeth Maillart, HAL-SU, Gestionnaire, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Multiple Sclerosis, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Context (language use), Gut flora, digestive system, Article, Flow cytometry, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Immune system, Immunity, RNA, Ribosomal, 16S, medicine, Homeostasis, Humans, 030304 developmental biology, 0303 health sciences, biology, medicine.diagnostic_test, business.industry, Microbiota, Multiple sclerosis, Patient Acuity, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, medicine.disease, biology.organism_classification, Commensalism, Gastrointestinal Microbiome, Immunoglobulin A, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Neurology, Immunoglobulin G, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Bacteria
Abstract: ObjectiveBased on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.MethodsWe investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.ResultsWe show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = −0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).ConclusionsGut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.
Published: 2021
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35. Prévalence de la dénutrition et évaluation de l’efficacité d’une prise en charge nutritionnelle précoce chez les patients hospitalisés atteints du COVID-19

Author: Pauline Faucher, Alexis Mathian, Dorothée Bedock, Julie Couffignal, Jean-Michel Oppert, P. Bel Lassen, Jehane Fadlallah, Zahir Amoura, and L. Soares
Subjects: Gynecology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Nutrition and Dietetics, Coronavirus disease 2019 (COVID-19), business.industry, Co23, Endocrinology, Diabetes and Metabolism, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Internal Medicine, medicine, business
Abstract: L'infection par le SARS-Cov2 (COVID-19) s'associe a un risque majeur de denutrition Cependant, les donnees nutritionnelles chez les patients atteints de COVID-19 sont limitees Nos objectifs etaient : – d'evaluer la prevalence de la denutrition chez les patients hospitalises pour COVID-19 a j0 puis a j30 post-hospitalisation ;– d'etudier les liens entre denutrition et gravite de la maladie a l'admission ;– d'etudier l'impact de la denutrition sur une evolution defavorable de la maladie (transfert vers une unite de soins intensifs (USI) ou deces) ;– d'evaluer l'impact d'une prise en charge nutritionnelle precoce Tous les patients hospitalises pour COVID-19 dans le service de medecine interne du CHU Pitie-Salpetriere ont ete inclus du 21 mars au 24 avril 2020 (n = 114, 60,5 % d'hommes, âge : 59,9 ± 15,9 ans) L'etat nutritionnel de ces patients a ete defini en utilisant les criteres de la Haute Autorite de sante (HAS) 2019 Les caracteristiques cliniques, radiologiques et biologiques des patients atteints de COVID-19 ont ete comparees en fonction de leur statut nutritionnel Une regression logistique a ete utilisee pour evaluer les associations entre les parametres nutritionnels et l'evolution defavorable de la maladie Une prise en charge nutritionnelle precoce selon la perte de poids et d'appetit des patients (consistant a une alimentation enrichie, une prevention du syndrome de renutrition inappropriee, des complements nutritionnels oraux CNO et/ou une nutrition enterale NE), a ete mise en place des l'admission A j30 post-hospitalisation, les donnees nutritionnelles cliniques, biologiques, anthropometriques, ont ete collectees afin d'etudier l'evolution de l'etat nutritionnel La prevalence globale de la denutrition a j0 etait de 44,6 % (14,2 % de denutrition moderee, 30,4 % de denutrition severe) Celle-ci atteignait 66,7 % chez les patients provenant d'un service de reanimation Une hypoalbuminemie initiale etait associee a un risque plus eleve de transfert en unite de soins intensifs (pour 10 g/L d'albumine, OR [IC95 %] : 0,31 [0,1 ;0,7] ;p < 0,01) et ce, independamment de l'âge et de la CRP Apres prise en charge nutritionnelle (69 % de CNO et 2,6 % de NE), la prevalence de la denutrition a j30 post-hospitalisation etait de 20,6 % (15,2 % de denutrition moderee et 5,4 % de denutrition severe) A j30, on observait une masse musculaire basse selon impedancemetrie et une fonction musculaire alteree selon Handgrip chez 29,3 % des patients par rapport aux normes HAS La COVID-19 en service de medecine est associee a une forte prevalence de la denutrition, encore plus marquee chez les patients provenant d'une USI L'hypoalbuminemie a l'admission est associee a une evolution defavorable de la maladie, et ce independamment de la CRP et de l'âge Un depistage et une prise en charge nutritionnelle globale est possible (malgre les difficultes de recueil de donnees anthropometriques et de mise en place de la strategie nutritionnelle liees aux mesures barriere), necessaire et efficace chez ces patients, de maniere precoce, ainsi que dans le suivi [ABSTRACT FROM AUTHOR] Copyright of Nutrition Clinique et Metabolisme is the property of Elsevier B V and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
Published: 2021

36. Analysis of bacterial-surface-specific antibodies in body fluids using bacterial flow cytometry

Author: Jehane Fadlallah, Kathrin Moor, Andrew J. Macpherson, Delphine Sterlin, Guy Gorochov, Maria L. Balmer, Albulena Toska, Emma Slack, and Martin Larsen
Subjects: 0301 basic medicine, Lysis, Clinical Chemistry Tests, Signal-To-Noise Ratio, Biology, General Biochemistry, Genetics and Molecular Biology, Antibacterial antibody, Flow cytometry, Microbiology, 03 medical and health sciences, Antibody Specificity, medicine, Humans, medicine.diagnostic_test, Bacterial pathogenesis, Flow Cytometry, biology.organism_classification, Antibodies, Bacterial, Primary and secondary antibodies, Body Fluids, 3. Good health, Blot, 030104 developmental biology, biology.protein, Antibody, Bacteria
Abstract: Antibacterial antibody responses that target surfaces of live bacteria or secreted toxins are likely to be relevant in controlling bacterial pathogenesis. The ability to specifically quantify bacterial-surface-binding antibodies is therefore highly attractive as a quantitative correlate of immune protection. Here, binding of antibodies from various body fluids to pure-cultured live bacteria is made visible with fluorophore-conjugated secondary antibodies and measured by flow cytometry. We indicate the necessary controls for excluding nonspecific binding and also demonstrate a cross-adsorption technique for determining the extent of cross-reactivity. This technique has numerous advantages over standard ELISA and western blotting techniques because of its independence from scaffold binding, exclusion of cross-reactive elements from lysed bacteria and ability to visualize bacterial subpopulations. In addition, less than 10(5) bacteria and less than 10 μg of antibody are required per sample. The technique requires 3-4 h of hands-on experimentation and analysis. Moreover, it can be combined with automation and mutliplexing for high-throughput applications.
Published: 2016
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37. Des lymphocytes B mémoires avec un phénotype unique persistent dans la rate de patients traités par rituximab au cours de la thrombopénie immunologique de l’adulte

Author: Etienne Crickx, Marc Michel, Imane Azzaoui, Etienne Rivière, Sébastien Storck, C.A. Reynaud, Jehane Fadlallah, Véronique Meignin, J.C. Weill, Bertrand Godeau, R. Geoffrey, G. Bonnard, Sandra K. Weller, Tatiana Fadeev, Aurélien Sokal, A. Vandenberghe, Matthieu Mahevas, and Pascal Chappert
Subjects: Gastroenterology, Internal Medicine
Abstract: Introduction Au cours de la thrombopenie immunologique (PTI), la depletion lymphocytaire B observee dans le sang peripherique apres rituximab (RTX) est habituellement complete. Ceci contraste avec des donnees obtenues au laboratoire suggerant que des lymphocytes B memoires ayant resiste au RTX peuvent participer aux rechutes a distance du traitement. Patients et methodes Afin de rechercher la presence eventuelle de lymphocytes B residuels apres RTX, nous avons analyse les tissus spleniques de patients splenectomises pour un echec du RTX. Les populations lymphocytaires B residuelles ont ete caracterisees sur le plan phenotypique en cytometrie en flux, et leur programme transcriptionnel a ete etudie par RNAseq en cellule unique. Nous avons egalement etudie les capacites fonctionnelles de ces cellules in vitro ainsi que leur reactivite envers la GPIIbIIIa. Resultats Nous avons etudie les tissus spleniques de 16 patients en echec du RTX (delai de 1 a 6 mois apres la derniere injection). Des lymphocytes B residuels, majoritairement de phenotype memoire, etaient presents en nombre significatif chez la moitie d’entre eux. Ces cellules presentaient un phenotype atypique avec une expression reduite de l’immunoglobuline et des molecules de surface associees au BCR, ne repondaient pas a la stimulation par le BCR, mais proliferaient apres stimulation CD40L permettant d’identifier apres culture et differenciation in vitro une reactivite anti-GPIIbIIIa pour certaines d’entre elles. L’analyse transcriptionnelle par RNAseq en cellule unique des lymphocytes B memoires mettait en evidence un programme d’expression unique, different des patients non traites par le rituximab ou des donneurs d’organes. Ce programme etait principalement caracterise par la surexpression de genes anti-apoptotiques, la sous-expression de genes impliques dans l’identite lymphocytaire B, et l’expression de molecules de surface pouvant potentiellement permettre de developper de nouvelles cibles therapeutiques. Conclusion En conclusion, l’ensemble de ces donnees a mis en evidence que des lymphocytes B memoires avec un phenotype unique resistent au RTX et peuvent persister dans la rate plusieurs mois apres le traitement, contribuant ainsi aux rechutes observees a distance du RTX.
Published: 2020
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38. From Dysgammaglobulinemia to Autosomal-Dominant Activation-Induced Cytidine Deaminase Deficiency: Unraveling an Inherited Immunodeficiency after 50 Years

Author: Florence Morin, Jehane Fadlallah, Cécile Masson, Aurore Pouliet, Loic Chentout, Bertrand Boisson, Anne Durandy, Sven Kracker, Eric Oksenhendler, and Jean-Laurent Casanova
Subjects: Hyper IgM syndrome, biology, business.industry, Nonsense mutation, Cytidine deaminase, medicine.disease, Molecular biology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, Immunochemistry, medicine, Activation-induced (cytidine) deaminase, biology.protein, 030212 general & internal medicine, Dysgammaglobulinemia, business, Immunodeficiency
Abstract: The genetic investigation of a family presenting with a dominant form of hyper IgM syndrome published in 1963 and 1975 revealed a R190X nonsense mutation in activation-induced cytidine deaminase. This report illustrates the progress made over 6 decades in the characterization of primary immunodeficiencies, from immunochemistry to whole-exome sequencing.
Published: 2020
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39. FRI0157 EPSTEIN BARR VIRUS BLOOD REPLICATION INCREASES DURING ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

Author: Fleur Cohen, Alexis Mathian, Sonia Burrel, Paul Breillat, Miguel Hie, Zahir Amoura, Vincent Calvez, Flore Rozenberg, David Boutolleau, M. Pineton De Chambrun, and Jehane Fadlallah
Subjects: medicine.medical_specialty, Cytopenia, Lupus erythematosus, Systemic lupus erythematosus, business.industry, Immunology, Hydroxychloroquine, medicine.disease, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Prednisone, Internal medicine, medicine, Immunology and Allergy, Seroconversion, skin and connective tissue diseases, business, Serositis, Viral load, medicine.drug
Abstract: Background:A role for Epstein Barr Virus (EBV) infection in Systemic Lupus Erythematosus (SLE) pathogenesis is highly suspected. The frequency of EBV seroprevalence and DNA detection in peripheral blood mononuclear cells are increased in SLE patients compared to healthy controls.Objectives:To analyse the relationship between EBV blood replication and SLE disease activity.Methods:Monocentric, observational and retrospective study of SLE patients (ACR or SLICC criteria) who have had a blood EBV DNA assessment using Polymerase Chain Reaction (artus® EBV Virus QS-RGQ assay) between 2012 and 2018. Exclusion criteria were: organ or bone marrow transplant, absence of EBV seroconversion and insufficient data. SLE clinical features, the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) flare index (SFI) and therapeutic regimen on the day of EBV DNA load assessment were recorded. A SELENA-SLEDAI score > 4 defined an active SLE. A blood EBV DNA load ≥125 IU/mL was defined as elevated.Results:A total of 105 patients (98 women and 7 men) were included in the study. At inclusion, median (quartiles) age and SLE duration were 34 (23.5-43) and 7 (2-14) years old, respectively. Treatment were hydroxychloroquine (HCQ) (n = 67; 64%), prednisone (n = 66; 63%) with an average (±Standard Deviation) dose of 11.3 (±16) mg/day and an immunosuppressant (n = 42; 40%). According to SFI, 57 SLE patients were experiencing a flare at the time of EBV assessment; flares were classified as severe and mild/moderate in 38 (36%) and 19 (18%) SLE patients, respectively. According to the SELENA-SLEDAI score, 60 patients (57%) were deemed active and 45 (43%) inactive. Main clinical manifestations were arthritis in 32 (30%) patients, constitutional symptoms (fever, weight loss, anorexia or lymphadenopathy) in 31 (30%), cutaneous involvement in 23 (22%), glomerulonephritis in 19 (18%), cytopenia in 14 (13%), neuropsychiatric involvement in 13 (12%) and serositis in 10 (16%). Blood EBV DNA was elevated in 54 (90%) of the 60 patients with active lupus versus 6 (13%) of the 45 patients with inactive SLE (p -4). It was increased in 34 (89%) of the 38 patients with severe flare, in 17 (89%) of the 19 patients with a mild/moderate flare (p = 1) and in 8 (17%) of the 48 patients without flare (p -4vs severe flare and p -4vs mild/moderate flare). EBV DNA load correlated with SELENA-SLEDAI score (r=0.58; p-4in paired analysis).Conclusion:Blood EBV viral load is dramatically increased in active phase of SLE, independently of the treatment. We were unable to demonstrate whether the replication of EBV was the cause or the consequence or just an epiphenomenon of the disease activity. Further studies are needed to study whether EBV viral load is linked with Interferons secretion or B lymphocyte activation.Disclosure of Interests:None declared
Published: 2020
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40. HHV8-related hemophagocytic syndrome: diagnosis is in the eye

Author: Lionel Galicier, Jean Edouard Martin, Sandrine Valade, and Jehane Fadlallah
Subjects: Adult, medicine.medical_specialty, business.industry, Pain medicine, Castleman Disease, HIV Infections, Critical Care and Intensive Care Medicine, Lymphohistiocytosis, Hemophagocytic, Anesthesiology, Emergency medicine, medicine, Humans, Female, business, Respiratory Insufficiency
Published: 2018

41. Microbial ecology perturbation in human IgA deficiency

Author: Lionel Galicier, Makoto Miyara, S. Dusko Ehrlich, Sean Kennedy, Zahir Amoura, Patricia Lepage, Martin Larsen, Jean-Paul Pais de Barros, Guy Gorochov, Doriane Gouas, Catherine Juste, Marion Malphettes, Delphine Sterlin, Jehane Fadlallah, Claire Fieschi, Alexis Mathian, Mathieu Almeida, David Boutboul, Nathalie Galleron, Florence Levenez, Joël Doré, Eric Oksenhendler, Nicolas Pons, Karim Dorgham, Gaëlle Autaa, Hela El Kafsi, Christophe Parizot, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Différenciation et progression tumorale des lymphocytes, École pratique des hautes études (EPHE)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), INRA US1367 MetaGenoPolis, King‘s College London, Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Maryland [College Park], University of Maryland System, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Universitaire d'Hématologie (IUH), 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), Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Université Paris Cité (UPCité), université de Bourgogne, LNC, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Immunoglobulin A, Colonization, Lipopolysaccharide, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Human gut microbiome, Systemic inflammation, medicine.disease_cause, Autoimmunity, 03 medical and health sciences, chemistry.chemical_compound, Immune system, Microbial ecology, medicine, Humans, Homeostasis, Innate, Immunoglobulin-a, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, biology, Bacteria, Microbiota, T-cells, IgA Deficiency, General Medicine, 3. Good health, 030104 developmental biology, chemistry, Immunoglobulin M, Immunology, biology.protein, Memory b-cells, Antibody, medicine.symptom, Secretory antibodies
Abstract: International audience; Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.
Published: 2018
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42. Étude clinique à long terme et mutations HAVCR2 chez 70 patients atteints de lymphome T sous cutané à type de panniculite

Author: Nicolas Ortonne, Jean-David Bouaziz, A. de Masson, Christine Bodemer, F. Comoz, R. Kerdraon, Michel D'Incan, G. Bohelay, Liliane Laroche, F. Brunet-Possenti, Stéphane Barete, Pauline Brice, Nathalie Franck, G. de Saint-Basile, Sylvie Fraitag, I. Beschet, Eve Maubec, Caroline Ram-Wolff, Fernando E. Sepulveda, I. Brocheriou, S. Laurent-Roussel, C. Bléchet, Laurence Lamant, B. Balme, P. Moguelet, Ambroise Marçais, Marisa Battistella, S. Oro, David Michonneau, A. Finon, Frédéric Guerin, N. Bonnet, François Skowron, Olivier Dereure, Guy Leverger, Serge Boulinguez, Béatrice Vergier, Felipe Suarez, G. Sonigo, D. Haidar, Marie Beylot-Barry, Gérard Socié, R. Dubois, F. Le Gall, A. Mahe, G. Hervé, Agnès Carlotti, E. Tournier, L. Deschamps, G. Bens, S. Taix, S. Faiz, V. Costes-Martineau, Vanessa Szablewski, O. Carpentier, Henri Adamski, E. Birckel, Stéphane Dalle, F. Franck, O. Augereau, Jehane Fadlallah, Martine Bagot, and Olivia Boccara
Subjects: Dermatology
Abstract: Introduction Les lymphomes T sous-cutanes a type de panniculite (SPTCL, subcutaneous panniculitis T cell lymphoma) sont une forme rare de lymphome T cutane d’evolution classiquement indolente, neanmoins certains patients ont une evolution agressive dont les determinants sont mal connus. Une etude recente a identifie une mutation germinale de HAVCR2 (codant pour TIM-3, recepteur d’inhibiteur de checkpoint) dans des cas familiaux de SPTCL, notamment dans des populations asiatiques et de l’Ocean Pacifique. La prevalence de cette mutation dans les cas sporadiques n’est pas connue. Le but de cette etude etait de decrire les caracteristiques cliniques, histologiques et le suivi d’une large cohorte de SPTCL et d’etudier la prevalence des mutations HAVCR2 dans les formes sporadiques. Materiel et methodes Les cas ont ete identifies dans la base de donnees du GFELC, le diagnostic confirme par un pathologiste expert du GFELC. Les donnees cliniques, histologiques et l’evolution ont ete recueillies apres un suivi median de 35 mois (5jours-22 ans). La mutation de TIM-3 etait recherchee par sequencage sur le tissu tumoral ou sur le sang. Resultats 70 cas ont ete inclus (55 femmes) d’âge median de 42 ans (1–90 ans). 37 % avaient un antecedent d’auto-immunite, notamment de lupus (38 %). La presentation clinique la plus frequente etait celle de petits nodules (1–5 cm) sous-cutanes multiples situes aux membres. Soixante-huit pourcent avaient des signes B associes. Un syndrome d’activation macrophagique (SAM), etait trouve chez 12 patients (18 %), dont 5 formes graves (pris en charge en soins intensifs). Des auto-anticorps ont ete detecte chez 62 % des patients, notamment des anticorps anti-nucleaires (58 %) ( image 1 ). Chez 9 patients, une forme histologique frontiere avec une panniculite lupique etait trouvee. L’analyse PCR a revele une mutation HAVCR2 chez 10/49 (20 %) des patients presentant un materiel lesionnel approprie (caractere germinal confirme pour 6 patients), d’origine cambodgienne, vietnamienne, caledonienne, tahitienne, marocaine, algerienne et de l’ocean Indien (inconnue dans 2). Le SAM etait plus frequent (4/10 versus 5/39) et significativement plus grave (3/10 versus 0, p = 0,006) chez les patients mutes. La plupart des patients ont recu un traitement immunomodulateur en 1ere ligne (76,5 %; image 2 ); les patients atteints de SAM severe ont necessite une greffe autologue de cellules souches ou une chimiotherapie a base d’etoposide. Sur les 67 patients avec des donnees de suivi, 49 (73 %) etaient en reponse complete au dernier suivi, 32 % ont rechute (sans association significative avec une mutation de HAVCR2), 5 sont decedes, un (sans mutation de HAVCR2) de SPTCL. Conclusion Cette etude est la plus grande serie de SPTCL. Nos resultats mettent en evidence de rares mutations germinales de HAVCR2 dans le SPTCL sporadique, mais associees a des formes de SAM severe.
Published: 2019
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43. Sinusoidal Obstruction Syndrome: Warning About Autologous Stem Cell Transplantation Preceded by Regimens Containing Oxaliplatin

Author: Jean Philippe Richardet, Jehane Fadlallah, Luc Fornecker, Manel Bedoui, Sébastien Mulé, Sylvie Glaisner, David Sibon, Jerome Tamburini, Marie-Pierre Moles, Jehan Dupuis, Corinne Haouin, Pierre-Edouard Debureaux, Emmanuelle Tavernier, Daniel Azoulay, Julien Calderaro, Frédérique Kuhnowski, and Hervé Tilly
Subjects: Cisplatin, Cancer Research, Carmustine, medicine.medical_specialty, Hepatic veno-occlusive disease, business.industry, Hematology, Filgrastim, medicine.disease, Oxaliplatin, Granulocyte colony-stimulating factor, Surgery, Transplantation, Autologous stem-cell transplantation, Oncology, medicine, business, medicine.drug
Published: 2019
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44. Azacitidine in the treatment of therapy related myelodysplastic syndrome and acute myeloid leukemia (tMDS/AML): A report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM)

Author: Cecile Bally, Lionel Ades, Benoit de Renzis, Norbert Vey, Pascal Turlure, Caroline Dartigeas, Raphael Itzykson, Stéphane de Botton, François Dreyfus, Sylvain Thepot, Bruno Quesnel, Jehane Fadlallah, and Pierre Fenaux
Subjects: Adult, Male, Oncology, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, Pediatrics, Azacitidine, Therapy-related myelodysplastic syndrome, Cohort Studies, Young Adult, hemic and lymphatic diseases, Internal medicine, Complex Karyotype, Humans, Medicine, Radiation Injuries, neoplasms, Societies, Medical, Aged, Aged, 80 and over, Response rate (survey), business.industry, Antineoplastic Protocols, Myeloid leukemia, Neoplasms, Second Primary, Hematology, Middle Aged, Transplantation, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Cohort, Etiology, Female, France, business, medicine.drug
Abstract: The effect of azacitidine (AZA) in therapy related MDS and AML (t-MDS/AML) is not well established. 54 patients (42 t-MDS and 12 t-AML), 71% of whom had complex karyotype, received AZA for at least one cycle (median 4 cycles). The overall response rate (ORR) was 39% in the whole cohort and 62% in patients who received ≥4 cycles. One, 2 and 3 year OS was 36%, 14% and 8% respectively. Female gender (p=0.01) and ECOG 0-1 (p=0.04) were associated with significantly better OS, while karyotype and marrow blast percentage had no significant impact. By comparison with de novo MDS/AML treated in the same program, t-MDS/AML had a similar response rate (38% vs 45% in de novo MDS/AML, p=0.53), but significantly shorter OS (2 year OS of 14% vs 33.9%, p=0.0005). However, in a multivariate analysis performed in all patients (de novo and therapy related cases), only complex karyotype and high IPSS, and not etiology (i.e. de novo versus therapy related), had a significant impact on OS. Nine (15%) patients received allogeneic stem cell transplantation, 4 of whom were still alive.
Published: 2013
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45. Outcome of Acute Promyelocytic Leukemia (APL) in Children and Adolescents: An Analysis in Two Consecutive Trials of the European APL Group

Author: Xavier Thomas, Christian Recher, Hervé Dombret, Agnès Guerci, Norbert Vey, Bruno Cassinat, André Baruchel, Nadia Idres, Thierry Leblanc, Pierre Fenaux, Christine Chomienne, Miguel A. Sanz, Guy Leverger, Cecile Bally, Lionel Ades, Yves Bertrand, Alain Robert, Jehane Fadlallah, Emmanuel Raffoux, Sciences Po Grenoble - Institut d'études politiques de Grenoble (IEPG), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Pédiatrie Hématologique, Hôpital Robert Debré, Unite de Biologie Cellulaire, Hematology (IPC-Marseille), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Service d'hématologie clinique [Avicenne], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]
Subjects: Male, Cancer Research, Pediatrics, Time Factors, medicine.medical_treatment, MESH: Risk Assessment, MESH: Dose-Response Relationship, Drug, law.invention, MESH: Cause of Death, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, Randomized controlled trial, law, MESH: Child, Cause of Death, Antineoplastic Combined Chemotherapy Protocols, Medicine, Cumulative incidence, Child, MESH: Treatment Outcome, Cause of death, MESH: Middle Aged, Age Factors, Middle Aged, Prognosis, 3. Good health, Europe, MESH: Antineoplastic Combined Chemotherapy Protocols, Leukemia, Treatment Outcome, Oncology, MESH: Survival Analysis, Child, Preschool, 030220 oncology & carcinogenesis, Female, MESH: Neoplasm Recurrence, Local, Adult, Acute promyelocytic leukemia, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tretinoin, MESH: Drug Administration Schedule, Risk Assessment, MESH: Prognosis, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Humans, Survival analysis, MESH: Adolescent, MESH: Age Factors, Chemotherapy, MESH: Humans, MESH: Tretinoin, Dose-Response Relationship, Drug, business.industry, MESH: Time Factors, MESH: Child, Preschool, MESH: Adult, medicine.disease, Survival Analysis, MESH: Male, Clinical trial, MESH: Disease-Free Survival, MESH: Europe, Neoplasm Recurrence, Local, business, MESH: Female, MESH: Leukemia, Promyelocytic, Acute, 030215 immunology
Abstract: Purpose Acute promyelocytic leukemia (APL) is rare in children. All-trans-retinoic acid (ATRA) combined with chemotherapy, the reference treatment of APL, is generally considered to produce similar results in children and adults. However, previously published childhood APL studies have generally analyzed all patients age < 18 years as a group, without further dividing according to age. Patients and Methods We compared disease characteristics and outcomes of children (age ≤ 12 years), adolescents (13 to 18 years), and adults (> 18 years) included in two multicenter APL clinical trials (APL 93 and 2000 trials). Results Of the 833 patients age ≤ 60 years included in the two trials, 26 (3%), 58 (7%), and 749 (90%) were children, adolescents, and adults, respectively. Children had significantly higher baseline WBC counts (P < .001). The complete remission (CR) rate (92%, 100%, and 94.5%, respectively) and 5-year cumulative incidence of relapse (CIR; 28%, 20%, and 23%, respectively) did not differ between children, adolescents, and adults, whereas adolescents had significantly better overall survival (OS; 5-year OS, 93.6% v 80.4% in adults and 80.4% in children; P = .03). However, in children age ≤ 4 years, the 5-year CIR was 52%, compared with 17.6% in children age 5 to 12 years (P = .006), although most of the younger children who relapsed experienced durable salvage with autologous or allogeneic stem-cell transplantation. Conclusion Adolescents and children age > 4 years with APL treated with ATRA and chemotherapy have outcomes at least as favorable as those of adults. Younger children seem to experience more relapses and may require reinforcement of first-line treatment.
Published: 2012
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46. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

Author: Lucile Musset, Makoto Miyara, Alexis Mathian, Jehane Fadlallah, Laetitia Claër, Romain Jouenne, Fleur Cohen-Aubart, Julien Haroche, Guy Gorochov, Driss Chader, Zahir Amoura, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immunologie [CHU Pitié-Salpétrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Regulatory T cell, lcsh:Medicine, Arthritis, Peripheral blood mononuclear cell, Methylprednisolone, T-Lymphocytes, Regulatory, Young Adult, Prednisone, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Young adult, lcsh:Science, Infusions, Intravenous, Multidisciplinary, Lupus erythematosus, Dose-Response Relationship, Drug, business.industry, lcsh:R, Middle Aged, medicine.disease, Dose–response relationship, Endocrinology, medicine.anatomical_structure, Treatment Outcome, lcsh:Q, Female, business, medicine.drug, Follow-Up Studies, Research Article
Abstract: International audience; Background/PurposeA slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.MethodsWe prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.ResultsSeventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.ConclusionIV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.
Published: 2015
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47. Grossesse et lupus : pronostic en cas de glomérulonéphrite extra-membraneuse

Author: Z. Amoura, Alexis Mathian, N. Costedoat-Chalumeau, H. Bazanahary, D. Boutin-Le Thi Huong, J. Haroche, Moez Jallouli, Makoto Miyara, D. Vauthier, Baptiste Hervier, Jehane Fadlallah, and J.C. Piette
Subjects: Gastroenterology, Internal Medicine
Published: 2010
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48. AZA In the Treatment of Therapy Related MDS and AML (tMDS/AML): a Report on 60 Patients by the Groupe Francophone Des Syndromes Myelodysplasiques (GFM)

Author: Cecile Bally, Norbert Vey, Pierre Fenaux, Caroline Dartigeas, Raphael Itzykson, Lionel Ades, Bruno Quesnel, Benoit de Renzis, Jehane Fadlallah, Sylvain Thepot, Pascal Turlure, François Dreyfus, and Stéphane de Botton
Subjects: medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Incidence (epidemiology), Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Chemotherapy regimen, Surgery, Discontinuation, Refractory, Internal medicine, Cohort, medicine, Lung transplantation, business, Myelofibrosis
Abstract: Abstract 2911 Background: AZA gives 50–60% responses and improves OS in higher-risk MDS but its role in t MDS/AML, characterized by a high frequency of unfavorable karyotypes and poor response to available treatments, remains unknown. Methods: An AZA compassionate program (ATU) was opened in France between Dec 2004 and Jan 2009 for higher risk MDS, and for AML not candidates to or refractory to intensive chemotherapy (IC). We analyzed t MDS/AML included in this program and having received at least 1 cycle of AZA, excluding patients (pts) previously treated with chemotherapy (CT) for their tMDS/AML. Results: 60 tMDS/AML were included: M/F:24/36, median age 69 (range 20–87). Primary disease was Breast Carcinoma (n=17), CLL (n=6), Hodgkin's disease (n=4), NHL (n=7), ALL (n=2), ovarian (n=2), liver(n=2), prostate carcinoma (n=2), other cancers (n=16), immunosuppressive therapy for lupus or Lung transplant in the last 2 pts. Treatment of primary neoplasm consisted in C×T in 86% and R×T in 61%. Diagnosis (WHO) was RCMD+/− RS in 4 pts, RAEB-1 in 10 pts, RAEB-2 in 28 pts MDS with myelofibrosis in 1 pt, and AML in 17 pts (including 12 FAB RAEBt). IPSS cytogenetics were fav in 4 (6.7%), int in 11 (18.3%), and unfav in 45 (75%, including 71% Complex karyotypes). Patients received a median of 4 cycles (range 1–24) of AZA, at FDA/EMEA-approved schedule (75 mg/m2/d ×7d/4 week) in 73% patients and a less intensive schedule (5d/4w, or 4 cycles, ORR was 21/35 (60%). Age, WBC count, baseline platelet count, % marrow blasts, karyotype (whatever the categorization) and ECOG status had no impact on ORR. 1, 2 and 3 year survival was 35%, 15% and 7%. Female gender (p=0.02), achievement of response (p=0.003) and ECOG status (0-1 vs 2–4) (p=0.04) had significant impact on OS while karyotype and % marrow blasts had no impact. However, there was a trend for lower OS in patients with chrom 5 abn (2y 0S 7.7% vs 23 %, p=0.08). 9 (15%) patients, all females, median age 55 (range 35–66) were allografted after a median number of 6 AZA cycles (range 2–17), including 3 pts, 4 pts and 2 pts who had achieved CR, mCR and no response to AZA, respectively. 4 (44%) of them were alive after 5+,17+,32+ and 42+ months. By comparison to the 232 pts with de novo MDS/AML included in the same program, tMDS/AML had a higher frequency of complex karyotype (71 vs 29.5, p Conclusion: In this cohort of tMDS/AML, survival with AZA was shorter than in de novo MDS/AML, probably largely due to their more severe baseline characteristics. Only 15% of tMDS/AML could be allografted, half of them with so far a favorable outcome. Disclosures: Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.
Published: 2010
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49. Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine

Author: Bertrand Godeau, Julien Rohmer, Damien Sène, Pascal Sève, Philippe Remy, Noël Zahr, Nans Florens, Romain Euvrard, Jean Baptiste Palluy, Matthieu Mahévas, Mathilde Roumier, Julien Haroche, Fleur Cohen-Aubart, Etienne Rivière, Hans Yssel, Audrey Barrelet, Jean François Viallard, Alexis Mathian, Jehane Fadlallah, Mathilde Devaux, Jean Simon Virot, Neila Benameur, Laurent Juillard, Cecile Chauvet, Blanca Amador-Borrero, Zahir Amoura, Michel Delahousse, Raphael Lhote, Micheline Pha, Capucine Morélot-Panzini, T. Chazal, Gaelle Richard-Colmant, Thibault Maillet, Laurent Perard, Miguel Hie, Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], 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 médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Foch [Suresnes], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Grand Hôpital de l'Est Francilien (GHEF), Centre hospitalier Saint Joseph - Saint Luc [Lyon], CHI Poissy-Saint-Germain, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier Les Chanaux [Mâcon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Henri Mondor, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Henri Mondor, Gestionnaire, Hal Sorbonne Université, 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 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)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service de pharmacologie médicale [CHU Pitié-Salpêtrière]
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, hydroxychloroquine, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Immunology, Lupus nephritis, Context (language use), Disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, skin and connective tissue diseases, Pandemics, ComputingMilieux_MISCELLANEOUS, Aged, 030203 arthritis & rheumatology, lupus nephritis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, COVID-19, Outbreak, Hydroxychloroquine, Middle Aged, systemic, medicine.disease, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, Female, Coronavirus Infections, business, Rheumatism, lupus erythematosus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) represents a source of concern for the management of patients with systemic lupus erythematosus (SLE). Indeed patients with SLE have an increased risk of severe infections due to intrinsic perturbations of their immune response, the use of immunosuppressive drugs, as well as the potential presence of organ damage associated with their disease. In this context, hydroxychloroquine (HCQ), a drug that is currently part of the long-term, standard-of-care treatment for SLE, has been reported to possess antiviral activity in vitro, and recent results from a preliminary clinical trial might support its use in curative or even prophylactic treatment for COVID-19.1–3 During the first days of the COVID-19 outbreak in France, we launched an observational study with the aim to follow the clinical course of COVID-19 in patients with SLE who received long-term treatment with HCQ. To be eligible, patients with SLE had to (1) fulfil the 1997 criteria of the SLE classifications of the American College of Rheumatology or those of the 2019 European League Against Rheumatism/American College of Rheumatology4 5; (2) be on long-term treatment with HCQ; and (3) have SARS-CoV-2 carriage in their nasopharyngeal swab, as confirmed by real-time reverse transcription PCR analysis. Data …
Published: 1970
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50. Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia

Author: Pascal Chappert, Sylvain Audia, Geoffrey Rossi, Jehane Fadlallah, Véronique Meignin, Marc Michel, Matthieu Mahévas, Etienne Rivière, Sébastien Storck, Sandra K. Weller, Etienne Crickx, Imane Azzaoui, Tatiana Fadeev, Claude-Agnès Reynaud, Alexis Vandenberghe, Jean-Claude Weill, Bertrand Godeau, Guillaume Bonnard, Aurélien Sokal, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris - UFR Médecine [Santé] (UP Médecine), and Université de Paris (UP)
Subjects: 0301 basic medicine, Immunoglobulin gene, [SDV]Life Sciences [q-bio], Naive B cell, Plasma cell, CD19, Article, 03 medical and health sciences, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Recurrence, medicine, Humans, B cell, CD20, B-Lymphocytes, Purpura, Thrombocytopenic, Idiopathic, biology, business.industry, Germinal center, General Medicine, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, biology.protein, Rituximab, business, medicine.drug
Abstract: International audience; Rituximab (RTX), an antibody targeting CD20, is widely used as a first-line therapeutic strategy in B cell–mediated autoimmune diseases. However, a large proportion of patients either do not respond to the treatment or relapse during B cell reconstitution. Here, we characterize the cellular basis responsible for disease relapse in secondary lymphoid organs in humans, taking advantage of the opportunity offered by therapeutic splenectomy in patients with relapsing immune thrombocytopenia. By analyzing the B and plasma cell immunoglobulin gene repertoire at bulk and antigen-specific single-cell level, we demonstrate that relapses are associated with two responses coexisting in germinal centers and involving preexisting mutated memory B cells that survived RTX treatment and naive B cells generated upon reconstitution of the B cell compartment. To identify distinctive characteristics of the memory B cells that escaped RTX-mediated depletion, we analyzed RTX refractory patients who did not respond to treatment at the time of B cell depletion. We identified, by single-cell RNA sequencing (scRNA-seq) analysis, a population of quiescent splenic memory B cells that present a unique, yet reversible, RTX-shaped phenotype characterized by down-modulation of B cell–specific factors and expression of prosurvival genes. Our results clearly demonstrate that these RTX-resistant autoreactive memory B cells reactivate as RTX is cleared and give rise to plasma cells and further germinal center reactions. Their continued surface expression of CD19 makes them efficient targets for current anti-CD19 therapies. This study thus identifies a pathogenic contributor to autoimmune diseases that can be targeted by available therapeutic agents.
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