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1. P1613: REAL-WORLD USE OF FOSTAMATINIB IN FRANCE. INTERIM RESULTS OF A NATIONAL REGISTRY.

Author

Guillaume Moulis, Matthieu Mahévas, Jean Francois Viallard, Sylvain Audia, Mikael Ebbo, Louis Terriou, Cheze Stephane, Thomas Moulinet, Thibault Comont, Clément Gourchechon, Philippe Guilpain, Ailsa Robbins, Manuela Rueter, Maryse Lapeyre-Mestre, Marc Michel, Bernard Bonnotte, and Bertrand Godeau

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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2. Qualitative monitoring of SARS-CoV-2 mRNA vaccination in humans using droplet microfluidics

Author

Matteo Broketa, Aurélien Sokal, Michael Mor, Pablo Canales-Herrerias, Angga Perima, Annalisa Meola, Ignacio Fernández, Bruno Iannascoli, Guilhem Chenon, Alexis Vandenberghe, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Marija Backovic, Felix A. Rey, Jean Baudry, Natalia T. Freund, Matthieu Mahévas, and Pierre Bruhns

Subjects
Immunology, Vaccines, Medicine
Abstract

SARS-CoV-2 mRNA vaccination generates protective B cell responses targeting the SARS-CoV-2 spike glycoprotein. Whereas anti-spike memory B cell responses are long lasting, the anti-spike humoral antibody response progressively wanes, making booster vaccinations necessary for maintaining protective immunity. Here, we qualitatively investigated the plasmablast responses by measuring from single cells within hours of sampling the affinity of their secreted antibody for the SARS-CoV-2 spike receptor binding domain (RBD) in cohorts of BNT162b2-vaccinated naive and COVID-19–recovered individuals. Using a droplet microfluidic and imaging approach, we analyzed more than 4,000 single IgG-secreting cells, revealing high interindividual variability in affinity for RBD, with variations over 4 logs. High-affinity plasmablasts were induced by BNT162b2 vaccination against Hu-1 and Omicron RBD but disappeared quickly thereafter, whereas low-affinity plasmablasts represented more than 65% of the plasmablast response at all time points. Our droplet-based method thus proves efficient at fast and qualitative immune monitoring and should be helpful for optimization of vaccination protocols.

Published
2023
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3. Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments

Author

Sylvain Audia, Matthieu Mahévas, Martin Nivet, Sethi Ouandji, Marion Ciudad, and Bernard Bonnotte

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells by their antigen-presenting functions. Moreover, the activation of the classical complement pathway participates to platelet opsonization and also to their destruction by complement-dependent cytotoxicity. Platelet destruction is also mediated by a FcγR-independent pathway, involving platelet desialylation that favors their binding to the Ashwell-Morell receptor and their clearance in the liver. Cytotoxic T cells also contribute to ITP pathogenesis by mediating cytotoxicity against megakaryocytes and peripheral platelets. The deficient megakaryopoiesis resulting from both the humoral and the cytotoxic immune responses is sustained by inappropriate levels of thrombopoietin, the major growth factor of megakaryocytes. The better understanding of ITP pathogenesis has provided important therapeutic advances. B cell-targeting therapies and thrombopoietin-receptor agonists (TPO-RAs) have been used for years. New emerging therapeutic strategies that inhibit FcγR signaling, the neonatal Fc receptor or the classical complement pathway, will deeply modify the management of ITP in the near future.

Published
2021
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4. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial

Author

Matthieu Mahévas, Imane Azzaoui, Etienne Crickx, Florence Canoui-Poitrine, Delphine Gobert, Laetitia Languille, Nicolas Limal, Constance Guillaud, Laure Croisille, Mohamed Jeljeli, Fréderic Batteux, Samia Baloul, Olivier Fain, France Pirenne, Jean-Claude Weill, Claude-Agnès Reynaud, Bertrand Godeau, and Marc Michel

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at one year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single arm, prospective phase 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety.

Published
2020
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8. Antibodies as drugs—a Keystone Symposia report

Author

Jennifer Cable, Erica Ollmann Saphire, Adrian C. Hayday, Timothy D. Wiltshire, Jarrod J. Mousa, David P. Humphreys, Esther C. W. Breij, Pierre Bruhns, Matteo Broketa, Genta Furuya, Blake M. Hauser, Matthieu Mahévas, Andrea Carfi, Tineke Cantaert, Peter D. Kwong, Prabhanshu Tripathi, Jonathan H. Davis, Neil Brewis, Bruce A. Keyt, Felix L. Fennemann, Vincent Dussupt, Arvind Sivasubramanian, Philip M. Kim, Reda Rawi, Eve Richardson, Daniel Leventhal, Rachael M. Wolters, Cecile A. W. Geuijen, Matthew A. Sleeman, Niccolo Pengo, and Francesca Rose Donnellan

Subjects
History and Philosophy of Science, General Neuroscience, General Biochemistry, Genetics and Molecular Biology
Abstract

Therapeutic antibodies have broad indications across diverse disease states, such as oncology, autoimmune diseases, and infectious diseases. New research continues to identify antibodies with therapeutic potential as well as methods to improve upon endogenous antibodies and to design antibodies de novo. On April 27-30, 2022, experts in antibody research across academia and industry met for the Keystone symposium "Antibodies as Drugs" to present the state-of-the-art in antibody therapeutics, repertoires and deep learning, bispecific antibodies, and engineering.

Published
2022
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9. Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience

Author

Etienne Crickx, Mikael Ebbo, Etienne Rivière, Odile Souchaud‐Debouverie, Louis Terriou, Sylvain Audia, Marc Ruivard, Bouchra Asli, Jean‐Pierre Marolleau, Nadine Méaux‐Ruault, Mathieu Gerfaud‐Valentin, Philippe Audeguy, Mohamed Hamidou, Selim Corm, Xavier Delbrel, Jean Fontan, Delphine Lebon, Christelle Mausservey, Guillaume Moulis, Nicolas Limal, Marc Michel, Bertrand Godeau, Matthieu Mahévas, 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), 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), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Edouard Herriot-Lyon, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne (Med Int - BESANCON), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Medipole De Savoie, Service de Médecine Interne [Pau], Centre hospitalier de Pau, Service d'hématologie, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
ITP, TPO-RA, Hematology, immunosuppressive drug, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, combination therapy
Abstract

International audience; Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.

Published
2023
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10. Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2– Recovered Dialysis Patients

Author

Philippe Attias, Imane Azzaoui, Khalil El Karoui, Andréa de La Selle, Aurélien Sokal, Pascal Chappert, Philippe Grimbert, Ignacio Fernandez, Magali Bouvier, Chloé Samson, Djamal Dahmane, Philippe Rieu, Patrice Nizard, Slim Fourati, Hamza Sakhi, and Matthieu Mahévas

Subjects
Vaccines, Synthetic, Transplantation, SARS-CoV-2, Epidemiology, Vaccination, Immunity, COVID-19, Antibodies, Viral, Critical Care and Intensive Care Medicine, Renal Dialysis, Nephrology, Immunoglobulin G, Humans, Original Article, mRNA Vaccines
Abstract

BACKGROUND AND OBJECTIVES: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti–SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2–recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2–recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal–Wallis test, or the Wilcoxon matched-pairs test as appropriate. RESULTS: In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses (P=0.008). In SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain–specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain–specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P

Published
2022
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13. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar

Subjects
medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Published
2022
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14. Primary immune thrombocytopenia in very elderly patients: particularities in presentation and management: results from the prospective CARMEN‐France Registry

Author

Guillaume Moulis, Daniel Adoue, Thibault Comont, Julien Maquet, Marc Michel, Nicolas Limal, Odile Beyne-Rauzy, Matthieu Mahévas, Bertrand Godeau, Thomas de Nadaï, and Aurélien Sokal

Subjects
Male, medicine.medical_specialty, genetic structures, Hemorrhage, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Prospective Studies, Aged, Aged, 80 and over, Data source, Purpura, Thrombocytopenic, Idiopathic, Platelet Count, business.industry, Age Factors, Anticoagulants, Disease Management, Hematology, Odds ratio, medicine.disease, Thrombosis, Confidence interval, Immune thrombocytopenia, Purpura, Female, France, medicine.symptom, Presentation (obstetrics), business
Abstract

Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to describe ITP in this subgroup. The data source was the prospective CARMEN-France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65-79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first-line treatment, need of second-line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex [odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31-17·32] and platelet count of

Published
2021
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15. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author

Aurélien Sokal, Paul Bastard, Pascal Chappert, Giovanna Barba-Spaeth, Slim Fourati, Alexis Vanderberghe, Pauline Lagouge-Roussey, Isabelle Meyts, Adrian Gervais, Magali Bouvier-Alias, Imane Azzaoui, Ignacio Fernández, Andréa de la Selle, Qian Zhang, Lucy Bizien, Isabelle Pellier, Agnès Linglart, Anya Rothenbuhler, Estelle Marcoux, Raphael Anxionnat, Nathalie Cheikh, Juliane Léger, Blanca Amador-Borrero, Fanny Fouyssac, Vanessa Menut, Jean-Christophe Goffard, Caroline Storey, Caroline Demily, Coralie Mallebranche, Jesus Troya, Aurora Pujol, Marie Zins, Pierre Tiberghien, Paul E. Gray, Peter McNaughton, Anna Sullivan, Jane Peake, Romain Levy, Laetitia Languille, Carlos Rodiguez-Gallego, Bertrand Boisson, Sébastien Gallien, Bénédicte Neven, Marc Michel, Bertrand Godeau, Laurent Abel, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Stuart G. Tangye, Jean-Laurent Casanova, Matthieu Mahévas, 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), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], 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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP. Nord - Université Paris Cité, Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université libre de Bruxelles (ULB), Hôpital Robert Debré, Centre Hospitalier le Vinatier [Bron], Hospital Universitario Infanta Leonor [Madrid], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Sydney Children's hospital, University of New South Wales [Sydney] (UNSW), Children’s Health Queensland [Brisbane] (CHQ), CHU Necker - Enfants Malades [AP-HP], Universidad Fernando Pessoa Canarias [Las Palmas de Gran Canaria, Spain], Garvan Institute of medical research, Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Funder(s): Agence Nationale de la Recherche Award Id(s): ANR-21-RHUS-0008, ANR-10-IAHU-01, ANR-10-LABX-62-IBEID , ANR-20-CE93-003Funder(s): Fondation pour la Recherche MédicaleAward Id(s): MEMO-COV-2-FRMFunder(s): Institut PasteurFunder(s): Agence Nationale de Recherches sur le Sida et les Hépatites ViralesFunder(s): Howard Hughes Medical InstituteFunder(s): Rockefeller UniversityFunder(s): St. Giles FoundationFunder(s): National Institutes of Health Award Id(s): R01AI088364, R01AI163029, UL1TR001866Funder(s): National Center for Advancing Translational SciencesFunder(s): Fisher Center for Alzheimer’s Research FoundationFunder(s): Meyer FoundationFunder(s): JPB FoundationFunder(s): French Foundation for Medical Research Award Id(s): EQU201903007798, EA20170638020Funder(s): European Union’s Horizon 2020 Award Id(s): 824110Funder(s): Square FoundationFunder(s): Fondation du SouffleFunder(s): French Ministry of Higher Education, Research, and Innovation Award Id(s): MESRI-COVID-19Funder(s): Institut National de la Santé et de la Recherche MédicaleFunder(s): Fondation Bettencourt SchuellerFunder(s): CSL BehringFunder(s): KU Leuven Award Id(s): C16/18/007Funder(s): http://dx.doi.org/10.13039/501100003130 Award Id(s): G0C8517N, G0B5120N, G0E8420NFunder(s): Jeffrey Modell FoundationFunder(s): National Health and Medical Research Council Award Id(s): 1176665Funder(s): Allergy and Immunology Foundation of AustraliaFunder(s): John Brown Cook FoundationFunder(s): Fondation Princesse GraceFunder(s): Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherchesFunder(s): Assistance Publique—Hôpitaux de Paris Award Id(s): MEMO-COV-2Funder(s): Société Nationale de Médecine InterneFunder(s): ANRS Nord-Sud Award Id(s): ANRS-COV05Funder(s): ANR-RHU Award Id(s): ANR-21-RHUS-08 (COVIFERON)Funder(s): HORIZON-HLTH-2021-DISEASE-04 Award Id(s): 01057100Funder(s): Grandir - Fonds de solidarité pour l’enfanceFunder(s): SCOR Corporate Foundation for ScienceFunder(s): REACTing-INSERMFunder(s): University of Paris CitéFunder(s): Imagine InstituteFunder(s): VIB GC PIDFunder(s): European Research Council Award Id(s): ERC-StG MORE2ADA2, ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CHU Henri Mondor

Subjects
EXPRESSION, COVID-19 Vaccines, Immunology, VECTOR, Research & Experimental Medicine, Antibodies, Viral, DISEASE, Immunology and Allergy, Humans, PSEUDOURIDINE, Autoantibodies, B-Lymphocytes, Science & Technology, SARS-CoV-2, Vaccination, COVID-19, Antibodies, Neutralizing, Medicine, Research & Experimental, Toll-Like Receptor 7, ANTIBODIES, Spike Glycoprotein, Coronavirus, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, mRNA Vaccines, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Life Sciences & Biomedicine
Abstract

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:220 issue:1 ispartof: location:United States status: published

Published
2023
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17. Molecular Signatures of Kidney Antibody–Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy

Author

Etienne Crickx, Selda Aydin, Alexandre Karras, Farah Tamirou, Jean-Claude Weill, Aurélie Hummel, Ailsa Robbins, Claude-Agnès Reynaud, Tatiana Fadeev, Frédéric Houssiau, Bernard Lauwerys, Tessa Huscenot, Nathalie Costedoat-Chalumeau, Matthieu Mahévas, Marion Rabant, Philippe Remy, Véronique Le Guern, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service d'anatomie pathologique, and UCL - (SLuc) Service de rhumatologie

Subjects
endocrine system, Pathology, medicine.medical_specialty, animal diseases, Plasma Cells, Immunology, Lupus nephritis, Renal function, Urine, Kidney, Rheumatology, Biopsy, medicine, Humans, Immunology and Allergy, Prospective Studies, Antibody-Producing Cells, Systemic lupus erythematosus, medicine.diagnostic_test, business.industry, Gene Expression Profiling, hemic and immune systems, Induction Chemotherapy, medicine.disease, Lupus Nephritis, eye diseases, Treatment Outcome, medicine.anatomical_structure, Bone marrow, business, Multiplex Polymerase Chain Reaction, tissues, Nephritis, Immunosuppressive Agents, Follow-Up Studies
Abstract

OBJECTIVE: This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy. METHODS: We included patients with biopsy-proven active lupus nephritis and performed anti-CD138 staining of kidney biopsy samples to visualize ASCs. We performed single-cell gene expression profiling on sorted ASCs from fresh biopsy samples using multiplex reverse transcriptase-polymerase chain reaction. We used a gene set that allowed for the study of ASC maturation from plasmablasts to long-lived plasma cells. We quantified urine ASCs from untreated patients with lupus nephritis at diagnosis and after 6 months of prospective follow-up during induction therapy. RESULTS: The number of kidney CD138+ ASCs in 46 untreated patients with lupus nephritis was correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASCs from 3 untreated patients had a plasmablast molecular signature; in contrast, in 4 patients with refractory lupus nephritis, the kidney ASCs were mainly long-lived plasma cells, representing an ASC transcriptional profile similar to that in the bone marrow of 2 healthy donors. Some urine ASCs with a plasmablast signature were detected in patients with untreated active lupus nephritis. The presence of urine ASCs at 6 months was associated with treatment failure. CONCLUSION: Our results suggest potential for ASC-directed therapy in refractory lupus nephritis.

Published
2021
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18. Hematologic disorder–associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response

Author

Nagham Alouche, Niclas Setterblad, Amélie Bonaud, Karl Balabanian, Etienne Crickx, Valeria Bisio, Mélanie Khamyath, David H. McDermott, Matthieu Mahévas, Nicolas Dulphy, Philip M. Murphy, Marion Espéli, Vincent Rondeau, Rim Hussein-Agha, and Julie Nguyen

Subjects
Receptors, CXCR4, Immunobiology and Immunotherapy, Plasma Cells, Immunology, Mice, Transgenic, Biology, Biochemistry, CXCR4, Hypogammaglobulinemia, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Animals, Humans, Mechanistic target of rapamycin, 030304 developmental biology, Myelokathexis, 0303 health sciences, TOR Serine-Threonine Kinases, Cell Biology, Hematology, medicine.disease, Hematologic Diseases, 3. Good health, medicine.anatomical_structure, Gain of Function Mutation, biology.protein, Bone marrow, Antibody, WHIM syndrome, Signal Transduction, 030215 immunology
Abstract

The extrafollicular immune response is essential to generate a rapid but transient wave of protective antibodies during infection. Despite its importance, the molecular mechanisms controlling this first response are poorly understood. Here, we demonstrate that enhanced Cxcr4 signaling caused by defective receptor desensitization leads to exacerbated extrafollicular B-cell response. Using a mouse model bearing a gain-of-function mutation of Cxcr4 described in 2 human hematologic disorders, warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and Waldenström macroglobulinemia, we demonstrated that mutant B cells exhibited enhanced mechanistic target of rapamycin signaling, cycled more, and differentiated more potently into plasma cells than wild-type B cells after Toll-like receptor (TLR) stimulation. Moreover, Cxcr4 gain of function promoted enhanced homing and persistence of immature plasma cells in the bone marrow, a phenomenon recapitulated in WHIM syndrome patient samples. This translated in increased and more sustained production of antibodies after T-independent immunization in Cxcr4 mutant mice. Thus, our results establish that fine-tuning of Cxcr4 signaling is essential to limit the strength and length of the extrafollicular immune response.

Published
2021
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19. Safety of anti‐SARS‐CoV‐2 vaccination for patients with immune thrombocytopenia

Author

Matthieu Mahévas, Marc Michel, Bertrand Godeau, Antoine Briantais, Mikael Ebbo, Etienne Crickx, Laetitia Languille, Louis Terriou, Nicolas Limal, Guillaume Moulis, and Stephanie Guillet

Subjects
Adult, Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hemorrhage, ChAdOx1 nCoV-19, Correspondence, Humans, Medicine, Prospective Studies, BNT162 Vaccine, Aged, Aged, 80 and over, Covid‐19, Purpura, Thrombocytopenic, Idiopathic, Platelet Count, SARS-CoV-2, business.industry, COVID-19, SARS‐CoV, Hematology, Middle Aged, vaccines, Virology, Immune thrombocytopenia, Vaccination, ITP, Female, Safety, business, 2019-nCoV Vaccine mRNA-1273, Follow-Up Studies
Published
2021
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20. Rituximab and immune thrombocytopenia in adults: The state of knowledge 20 years later

Author

Bertrand Godeau, Matthieu Mahévas, and Samuel Deshayes

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Immune thrombocytopenia, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, medicine, Rituximab, business, 030215 immunology, medicine.drug
Abstract

Resume Le rituximab est utilise depuis pres de 20 ans dans le purpura thrombopenique immunologique (PTI), et est maintenant considere comme une option therapeutique valide en seconde ligne. Il a ete montre que 60–70 % des patients ont une reponse initiale au rituximab, mais la moitie rechutera. Ainsi, une cure de rituximab a 375 mg/m2/semaine pendant 4 semaines ou 1000 mg a 2 semaines d'intervalle permet un taux de reponse soutenue de 30 % a 5 ans dans les PTI persistants et chroniques. Malheureusement, il n'existe pas a ce jour de facteur predictif de reponse a long terme suffisamment robuste pour aider le medecin dans la decision therapeutique chez un individu donne. Le retraitement par rituximab est efficace, avec une reponse et une duree de reponse de meme ordre ou superieure chez la majorite des patients. Le rituximab est generalement bien tolere, avec principalement des effets secondaires lies a la perfusion d'intensite legere et facilement gerables. Les infections severes sont rares y compris a long terme, et surviennent chez des patients avec au moins un autre facteur predisposant dans plus de 2/3 des cas. Plusieurs questions restent encore a resoudre. Ainsi, des essais therapeutiques comparant directement le rituximab aux autres traitements du PTI et la mise en evidence de facteurs predictifs robustes de reponse a long terme sont necessaires pour mieux determiner la place du rituximab dans l'arsenal therapeutique du PTI. De plus, la place des traitements combines, d'un traitement de maintenance et du rituximab chez les PTI nouvellement diagnostiques meritent d'autres etudes.

Published
2021
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21. Prise en charge du purpura thrombopénique immunologique multiréfractaire

Author

Sylvain Audia, Jean-François Viallard, and Matthieu Mahévas

Subjects
business.industry, medicine.medical_treatment, Splenectomy, Gastroenterology, 030204 cardiovascular system & hematology, medicine.disease_cause, medicine.disease, Immune thrombocytopenia, Autoimmunity, 03 medical and health sciences, 0302 clinical medicine, Refractory, immune system diseases, hemic and lymphatic diseases, Immunology, Internal Medicine, medicine, Rituximab, business, Monoclonal gammopathy of undetermined significance, 030215 immunology, medicine.drug
Abstract

Multirefractory immune thrombocytopenia (ITP) is defined by the absence of response to TPO receptor agonists, rituximab and splenectomy (or contraindicated or refused) and the need of treatment. The approach to multirefractory ITP must be systematic and firstly involves reconsidering the diagnosis. Inherited thrombocytopenia, lymphoid hemopathies and myelodysplastic syndrome are the main causes to be mentioned. Multirefractory ITP is often associated with secondary ITP with signs of clinical or biological autoimmunity, monoclonal gammopathy of undetermined significance and a poor response to corticosteroids. Therapeutic management is complex and is based on the combination of treatments. New treatments are being developed.

Published
2021
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22. NSAID exposure delays time-to-pregnancy in patients with spondyloarthritis: an analysis of the GR2 prospective cohort

Author

Beatrice Banneville, Jérémie Sellam, François Goffinet, Nathalie Costedoat-Chalumeau, Anna Molto, Frédéric Lioté, Emmanuel Maheu, Amélie Denis, Anne-Sophie Korganow, Christelle Sordet, Emmanuelle Dernis, Martin Soubrier, Xavier Mariette, Christophe Richez, Laurent Perard, Nicolas Schleinitz, Patrick Jégo, Elisabeth Pasquier, Sabine Berthier, Claire Grange, Marc Lambert, Jonathan London, Hélène Maillard, François Maurier, Alexis Régent, Vincent Sobanski, Jacques Morel, Rene-Marc Flipo, Emanuelle Dernis, Alban Deroux, Marc Fabre, Marion Couderc, Nihal Martis, Martin Michaud, Raphaele Seror, Sophie Georgin-Lavialle, Léa Savey, Hervé Levesque, Jean-Loup Pennaforte, Rakiba Belkhir, Maria Letizia Urban, Sandra Desouches, Elisabeth Gervais, Augustin Latourte, Aline Frazier, Sabrina Hamroun, Matthieu Mahevas, Bertrand Godeau, Marc Michel, Cédric Lukas, Pascal Cathébras, Geoffrey Urbanski, Holy Bezanahary, Cecile Yelnik, Ygal Benhamou, Thierry Thomas, Nicolas Martin-Silva, Gaëlle Leroux, Veronique Le Guern, Claire Larroche, Emilie Berthoux, Fleur Cohen, Guillaume Direz, Nicole Ferreira-Maldent, Antoine Froissart, Vincent Langlois, Agnès Portier, Mélanie Roriz, Boris Bienvenu, Alice Berezne, Claire Cazalets, Aurelie Hummel, Pascal Coquerelle, Laurence Loeuillet, Noémie Jourde-Chiche, Claire Blanchard-Delaunay, Moez Jallouli, Cristina Belizna, Isabelle Durieu, Gaëlle Guettrot-Imbert, Catherine Deneux-Tharaux, Elisabeth Elefant, Laetitia Dunogeant, Anne Gompel, Lisa Biale, Agathe Masseau, Elodie Chauvet, Juliette Delforge, Christian Lavigne, Marie-Agnès Timsit, Delphine Lariviere, Evangeline Pillebout, Antoinette Perlat, Jean-Maxime Piot, Vassilis Tsatsaris, Mathilde de Menthon, Claire de Moreuil, Gaetan Sauvetre, Loïc Raffray, Jeremy Ora, Celine Lartigau-Roussin, Nathalie Tieulé, Sara Melboucy-Belkhir, Antoine Baudet, Constance Beaudouin-Bazire, Anne Calas, Olivia Chandesris, Jérémy Chatelais, Marine Driessen, Aurélie Du Thanh, Cécile Durant, Phillipe Goupille, Constance Guillaud-Danis, Stéphane Jobard, Laurence Josselin-Mahr, Thomas Le Gallou, Valentine Loustau, Hélène Petit Bauer, Vincent Poindron Geneviève Plu-Bureau, Jeremy Sellam, and Katia Stankovic-Stojanovic

Subjects
Medicine
Abstract

Background The impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in women with SpA and the factors influencing TTP in this population.Methods This prospective observational multicentre (63 centres) French cohort (GR2 study—NCT02450396) included consecutive women with a diagnosis of SpA (according to their rheumatologist) who wanted to become pregnant between 2015 and 2021. TTP (in months) was the main outcome criterion, prospectively calculated from the date of study inclusion to the date of conception. Data on demographics, disease characteristics, disease activity, severity and treatment were prospectively collected at inclusion and each year thereafter until pregnancy occurred. TTP and its associated factors were estimated by survival analysis (Shared Frailty Cox models), with a random centre effect and multiple imputation to address missing data.Results We analysed 88 women included before conception. Among them, 56 (63.6%) became pregnant during follow-up. Median TTP was 16.1 (95% CI (12.2 to 25.3)) months. Mean preconceptional Bath Ankylosing Spondylitis Disease Activity Index at inclusion was 2.9 (±SD 2.1). Patients were treated with TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs and glucocorticoids in 61 (69.3%), 23 (26.1%), 12 (13.6%) and 8 (9.1%) cases, respectively. The multivariate model found a significant association between TTP and age (HR) (per year) 1.22 95% CI (1.08 to 1.40); p

Published
2024
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23. Hepatic Sarcoidosis: Current Concepts and Treatments

Author

Dominique Valeyre, Marianne Ziol, Geoffrey Rossi, Dominique Roulot, and Matthieu Mahévas

Subjects
Liver Cirrhosis, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cirrhosis, Sarcoidosis, business.industry, Liver Diseases, Critical Care and Intensive Care Medicine, medicine.disease, Dermatology, Review article, 03 medical and health sciences, 0302 clinical medicine, Liver, 030220 oncology & carcinogenesis, Hypertension, Portal, Humans, Medicine, Portal hypertension, 030211 gastroenterology & hepatology, business, Liver pathology, Pathological, Hepatic sarcoidosis
Abstract

Hepatic sarcoidosis is a relatively common manifestation of extrapulmonary sarcoidosis. It occurs in 20 to 30% of cases and is rarely severe. However, a cluster of patients may develop severe complications such as cirrhosis and portal hypertension. In this review, we describe the current knowledge of clinical, biological, pathological, and radiological features of liver involvement in sarcoidosis and discuss essential clues for management and treatment.

Published
2020
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24. Characteristics, management and outcome of acquired amegakaryocytic thrombocytopenia

Author

Anais Roeser, Guillaume Moulis, Mikael Ebbo, Louis Terriou, Elsa Poullot, Bertrand Lioger, Marie Chilles, Helene Labussière‐Wallet, Christelle Mausservey, Micheline Pha, Mathieu Puyade, Stephane Cheze, Nicolas Limal, Marc Michel, Bertrand Godeau, and Matthieu Mahévas

Subjects
Purpura, Thrombocytopenic, Humans, Hematology, Bone Marrow Diseases, Megakaryocytes
Published
2022

25. De novo and relapsed immune thrombocytopenia after COVID-19 vaccines: results of French safety monitoring

Author

Guillaume, Moulis, Etienne, Crickx, Laure, Thomas, Nathalie, Massy, Matthieu, Mahévas, Marie-Blanche, Valnet-Rabier, Marina, Atzenhoffer, Marc, Michel, Bertrand, Godeau, Haleh, Bagheri, and Francesco, Salvo

Subjects
Purpura, Thrombocytopenic, Idiopathic, Vaccines, COVID-19 Vaccines, SARS-CoV-2, Immunology, COVID-19, Humans, Cell Biology, Hematology, Biochemistry, Thrombocytopenia
Published
2022

26. Dynamic Interactions Within the Splenic Niche and Long-Lasting Germinal Center Imprinting Define Human Anti-Vaccinia Long-Lived Memory B Cells

Author

Pascal Chappert, François Huetz, Marie-Alix Espinasse, Fabrice Chatonnet, Louise Pannetier, Lucie Da Silva, Clara Goetz, Jérôme Megret, Aurélien Sokal, Etienne Crickx, Ivan Nemazanyy, Vincent Jung, Chiara Guerrera, Sébastien Storck, Matthieu Mahévas, Antonio Cosma, Patrick Revy, Thierry Fest, Claude-Agnès Reynaud, and Jean-Claude Weill

Published
2022
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27. Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Author

Aurélien Sokal, Matteo Broketa, Giovanna Barba-Spaeth, Annalisa Meola, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas, 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), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Hôpital Henri Mondor, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris]-Université Paris Cité (UPCité), This work was initiated by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR and MEMO-COV-2-FRM) and funded by the Fondation Princesse Grace, an ERC Advanced Investigator Grant (B-response), and a grant from the French Ministry of Health (Soutien Exceptionnel à la Recherche Clinique 2022, CAPNET [Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherches]). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. Work in the Unit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur. A.S. was supported by a Poste d’accueil from INSERM, I.F. by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), M.B. by a CIFRE fellowship from the Association Nationale de la Recherche et de la Technologie (ANRT), and A.D.L.S by a SNFMI fellowship. P.B. acknowledges funding from the French National Research Agency grant ANR-14-CE16-0011 project DROPmAbs, the Institut Carnot Pasteur Microbes et Santé (ANR 11 CARN 0017-01), the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM)., We thank Garnett Kelsoe for providing the human cell culture system, together with invaluable advice, A. Boucharlat and the Chemogenomic and Biological Screening Core Facility headed by F. Agou, as well as P. England and the Molecular Biophysics Core Facility at the Institut Pasteur, Paris, France for their support during the course of this work, Sébastien Storck, Lucie Da Silva, and Sandra Weller for their advice and support, the physicians, Constance Guillaud, Raphael Lepeule, Frédéric Schlemmer, Elena Fois, Henri Guillet, Nicolas De Prost, and Pascal Lim, whose patients were included in this study, and Florence Guivel-Benhassine and Olivier Schwartz from the Institut Pasteur for providing authentic SARS-CoV-2 B.1.1.529 virus., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)

Subjects
B cells, MBC, variants, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Omicron, SARS-CoV-2, VOC, Immunology, Vaccination, COVID-19, Antibodies, Viral, Antibodies, Neutralizing, Infectious Diseases, mRNA vaccine, germinal center, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, memory B cells, Immunology and Allergy, Humans, affinity, RNA, Messenger, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract

International audience; The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant remains unclear. We assessed the affinity and neutralization potency against the Omicron variant of several hundred naturally expressed MBC-derived monoclonal IgG antibodies from vaccinated COVID-19-recovered and -naive individuals. Compared with other variants of concern, Omicron evaded recognition by a larger proportion of MBC-derived antibodies, with only 30% retaining high affinity against the Omicron RBD, and the reduction in neutralization potency was even more pronounced. Nonetheless, neutralizing MBC clones could be found in all the analyzed individuals. Therefore, despite the strong immune escape potential of the Omicron variant, these results suggest that the MBC repertoire generated by mRNA vaccines still provides some protection against the Omicron variant in vaccinated individuals.

Published
2022
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28. Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells

Author

Aurélien Sokal, Matteo Broketa, Annalisa Meola, Giovanna Barba-Spaeth, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, and Matthieu Mahévas

Abstract

SummaryMemory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.

Published
2021
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29. USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still’s Disease in Elderly Patients

Author

Achille Aouba, Julien Rossignol, Matthieu Mahévas, Damien Roos-Weil, Pierre Hirsch, Anna Sevoyan, Yervand Hakobyan, Sébastien Miranda, Louis Terriou, Julie Graveleau, Gwenola Maigne, Matthieu Groh, Thomas Quemeneur, Florent Malard, Marie Sebert, Sophie Georgin-Lavialle, Artem Oganesyan, Arsène Mekinian, Nabil Belfeki, Pierre Fenaux, Matthieu Decamp, Laurent Sailler, Louis Drevon, M. Delplanque, Jerome Razanamahery, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Saint-Nazaire, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre hospitalier Marc Jacquet (Melun), National Academy of Sciences of the Republic of Armenia [Yerevan] (NAS RA), Hôpital Foch [Suresnes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Génétique [CHU Caen], Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre hospitalier [Valenciennes, Nord], CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [CHU Saint-Antoine], HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], CHU Toulouse [Toulouse], and Service de Médecine Interne [CHU Saint-Antoine]

Subjects
medicine.medical_specialty, Chronic myelomonocytic leukemia, Disease, adult-onset Still's disease, SAID, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Internal medicine, hemic and lymphatic diseases, Atypia, USAID, adult-onset Still’s disease, Medicine, VEXAS, azacytidine, myelodysplastic syndrome, 030203 arthritis & rheumatology, Anakinra, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Myeloid leukemia, Retrospective cohort study, General Medicine, medicine.disease, Infliximab, 3. Good health, chemistry, 030220 oncology & carcinogenesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

International audience; Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

Published
2021
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30. Eltrombopag in adult patients with immune thrombocytopenia in the real-world in France, including off-label use before 6 months of disease duration: The multicenter, prospective ELEXTRA study

Author

Julia Moeglin, Morgane Mourguet, Laurent Alric, Laure Swiader, Suzanne Tavitian, Jean-Marc Durand, Sylvie Ollier, Aline Moignet‐Autrel, Karen Delavigne, Miguel Carreiro, Pierre Cougoul, Jean Estelle, Sylvain Audia, Benjamin De Sainte Marie, Veronique Remy, Xavier Delbrel, Samuel Deshayes, Francis Gaches, Helene Hennique, Lorraine Leplay, Gaetan Sauvetre, Antoine Briantais, Cécile Borel, Kamel Laribi, Martin Michaud, Stéphane Cheze, Sondess Hadj‐Khelifa, Guillaume Martin‐Blondel, Geoffrey Urbanski, Brice Castel, Guillaume Moulis, Fanny Nuccio, Soraya Leclerc-Teffahi, Odile Beyne‐Rauzy, Benjamin Hebraud, Aurelie Godel‐Labouret, Pierre Duffau, Sarah Khatibi, Baptiste Andre, Gregory Pugnet, Daniel Adoue, Julie Seguier, Clement Gaudin, Marc Michel, Myriam Aroichane, Laurent Prudhomme, Margaux Lafaurie, Manuela Rueter, Philippe Montane De La Roque, Natacha Brun, Aurelie Saunier, Julie Graveleau, Johanne Germain, Willy Vaillant, Agnès Sommet, Maryse Lapeyre-Mestre, Delphine Bonnet, Stephane Sire, Yann Leveneur, Caroline Soubrier, Alina Danu, Veronique Veit, Patrick Giraud, François Lifermann, Gwenola Maigne, Jean-François Viallard, Clothilde Martel, Nicolas Limal, Delphine Brechemier, Frederique Roy‐Peaud, Serge Madaule, Laurent Sailler, Thibault Comont, Benoit Faucher, Laurent Balardy, Carine Courtault, Claire Dingremont, Jean-Robert Harlé, Sophie Arista, Mikael Ebbo, Bertrand Godeau, Jeremie Dion, Bernard Bonnotte, Irène Machelart, Matthieu Mahévas, Nicolas Schleinitz, Arnaud Saint‐Lezer, Corentin Orvain, Christian Recher, Patrick Rispal, and Bertrand Lioger

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Disease duration, Eltrombopag, Off-label use, Benzoates, chemistry.chemical_compound, medicine, Humans, Prospective Studies, Aged, Purpura, Thrombocytopenic, Idiopathic, Adult patients, business.industry, Hematology, Off-Label Use, Middle Aged, Immune thrombocytopenia, Hydrazines, Treatment Outcome, chemistry, Pyrazoles, Female, France, business
Published
2021

31. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Author

Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa, Imane Azzaoui, Andréa de La Selle, Alexis Vandenberghe, Slim Fourati, Anais Roeser, Annalisa Meola, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Pirenne, Jérôme Mégret, Jean-Michel Pawlotsky, Simon Fillatreau, Pierre Bruhns, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Pascal Chappert, Matthieu Mahévas, 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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de bactériologie, virologie, hygiène [Mondor], Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Etablissement Français du Sang, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Inovarion, This work was initiated by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2 -FRM) and funded by the Fondation Princesse Grace and by an ERC Advanced Investigator Grant (B-response). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. Work in the Unit of Structural Virology was funded by the Institut Pasteur Urgence COVID-19 Fundraising Campaign. A.S. was supported by a Poste d’Accueil from the Institut National de la Santé et de la Recherche Médicale (INSERM), I.F. by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), M.B. by a CIFRE fellowship from the Association Nationale de la Recherche et de la Technologie (ANRT), and A.d.L.S by a SNFMI fellowship. P.B. acknowledges funding from ANR (ANR-14-CE16-0011–DROPmAbs), the Institut Carnot Pasteur Microbes et Santé (ANR 11 CARN 0017-01), the Institut Pasteur, and INSERM., We thank Garnett Kelsoe for providing the human cell culture system and invaluable advice. We thank A. Boucharlat and the Chemogenomic and Biological screening core facility headed by F. Agou as well as P. England and the Molecular Biophysics core facility at the Institut Pasteur, Paris, France for support during the course of this work. We also thank Sébastien Storck, Lucie Da Silva, and Sandra Weller for advices and support and the physicians, Constance Guillaud, Raphael Lepeule, Frédéric Schlemmer, Elena Fois, Henri Guillet, Nicolas De Prost, and Pascal Lim, whose patients were included in this study., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Immunology, Antibody Affinity, Immunization, Secondary, Somatic hypermutation, Antibodies, Viral, Mass Vaccination, Article, plasma cells, RBD, Affinity maturation, 03 medical and health sciences, 0302 clinical medicine, Memory B Cells, Animals, Humans, Immunology and Allergy, Potency, B-cell memory, RNA, Messenger, Neutralizing antibody, Memory B cell, BNT162 Vaccine, Cells, Cultured, 030304 developmental biology, affinity maturation, 0303 health sciences, BNT162b2 vaccine, biology, SARS-CoV-2, Precursor Cells, B-Lymphoid, Germinal center, COVID-19, neutralizing antibody, Convalescence, Antibodies, Neutralizing, 3. Good health, somatic hypermutation, Vaccination, Infectious Diseases, germinal center, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Immunologic Memory, 030217 neurology & neurosurgery
Abstract

In addition to serum immunoglobulins, memory B cell (MBC) generation against SARS-CoV-2 represents another layer of immune protection, but the quality of MBC responses in naive and COVID-19-recovered individuals after vaccination remains ill-defined. We studied longitudinal cohorts of naive individuals and disease-recovered patients for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of VDJ repertoires, affinity and neutralization against variants of concern (VOCs), using unbiased cultures of 2452 MBCs. Upon boosting, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOCs. Although naïve individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity towards multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs., Graphical Abstract, To better understand B cell responses to SARS-CoV-2 mRNA vaccination, Sokal et al. analyzed memory B cells from COVID-19-recovered and -naive individuals. In recovered patients, vaccination amplifies a broad repertoire of matured MBCs and generates variant-neutralizing plasma cells. In naïve individuals, vaccination induces an MBC pool containing potent neutralizing clones against all current variants of concern, including beta and delta.

Published
2021
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32. Mémoire immunitaire contre le SARS-CoV-2: Des anticorps contre l’infection initiale et des lymphocytes B à mémoire contre les infections futures

Author

Pascal Chappert, Claude-Agnès Reynaud, Matthieu Mahévas, Jean-Claude Weill, Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
0303 health sciences, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], General Medicine, Biology, Immunological memory, Virology, General Biochemistry, Genetics and Molecular Biology, 3. Good health, Vaccination, 03 medical and health sciences, 0302 clinical medicine, biology.protein, Antibody, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract

International audience

Published
2021
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33. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19

Author

Stanislas Faguer, Pierre Tiberghien, Etienne Crickx, Fanny Pommeret, David Veyer, Claire Rouzaud, Fabrice Camou, Olivier Hermine, Elie Azoulay, Pierre Gallian, Cécile Pouderoux, Deborah Eshagh, Jonathan London, Fatiha Merabet, Philippe Petua, David Boutboul, Laure Anne Raillon, Valérie Zeller, Hélène Péré, Benjamin Planquette, Jérôme Pacanowski, Adrien Joseph, Marc Michel, Martin Martinot, Matthieu Mahévas, Lucienne Chatenoud, Karine Lacombe, Anne Lise Beaumont, David Ghez, Amani Ouedrani, Tali Anne Szwebel, Arsène Mekinian, Florence Ader, Thomas Hueso, Marc Garnier, and Sébastien Clerc

Subjects
0301 basic medicine, Clinical Trials and Observations, Immunology, Pneumonia, Viral, Context (language use), 030204 cardiovascular system & hematology, Biochemistry, Immunoglobulin G, Serology, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Agammaglobulinemia, medicine, Humans, Adverse effect, Pandemics, COVID-19 Serotherapy, Autoimmune disease, B-Lymphocytes, biology, business.industry, SARS-CoV-2, Brief Report, Bacterial pneumonia, Immunization, Passive, COVID-19, Cell Biology, Hematology, medicine.disease, 3. Good health, Pneumonia, 030104 developmental biology, biology.protein, Antibody, business, Coronavirus Infections
Abstract

There is a Blood Commentary on this article in this issue., Key Points As a proof of concept, COVID-19 convalescent plasma represents an interesting approach in B-cell–depleted patients with protracted COVID-19.COVID-19 convalescent plasma induces a decrease in temperature and inflammatory parameters within 1 week associated with oxygen weaning., Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2., Visual Abstract

Published
2020

34. Monoclonal Gammopathy, Arthralgias, and Recurrent Fever Syndrome: A New Autoinflammatory Syndrome?

Author

Jean Baptiste Picque, Alexandre Terré, Sophie Georgin-Lavialle, Alexis Talbot, Serge Amselem, Irina Giurgea, Camille Louvrier, Matthieu Mahévas, Gilles Grateau, David Boutboul, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre Hospitalier d'Auxerre, CHU Henri Mondor, Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], French Network of Dysimmune Disorders Associated with Hemopathies, and Couvet, Sandrine

Subjects
Adult, Male, medicine.medical_specialty, Fever, Immunology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, PARAPROTEINEMIAS, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Recurrence, Median frequency, medicine, Humans, Immunology and Allergy, Aged, Retrospective Studies, 030203 arthritis & rheumatology, SCHNITZLER SYNDROME, business.industry, Antibodies, Monoclonal, INNATE IMMUNE RESPONSE, Retrospective cohort study, Syndrome, Middle Aged, medicine.disease, Autoinflammatory Syndrome, Paraproteinemias, Arthralgia, Dermatology, Interleukin 1 Receptor Antagonist Protein, Monoclonal gammopathy, C-Reactive Protein, Treatment Outcome, Schnitzler syndrome, Immunoglobulin M, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Recurrent fever, Immunoglobulin G, Female, medicine.symptom, business, Follow-Up Studies
Abstract

Objective.To describe a new autoinflammatory syndrome with recurrent fever and monoclonal gammopathy that differs from Schnitzler syndrome.Methods.We conducted a retrospective study of patients with monoclonal gammopathy and recurrent fever of unknown origin.Results.Five patients were studied; median age at onset of symptoms was 44 years. Median frequency of fever attacks was 6 episodes per year. In the absence of treatment, the median duration of fevers was 3 days.Conclusion.This new autoinflammatory syndrome is defined by an association among monoclonal gammopathy, arthralgias, and recurrent fever.

Published
2019
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35. Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting

Author

Pascal Chappert, François Huetz, Marie-Alix Espinasse, Fabrice Chatonnet, Louise Pannetier, Lucie Da Silva, Clara Goetz, Jérome Mégret, Aurélien Sokal, Etienne Crickx, Ivan Nemazanyy, Vincent Jung, Chiara Guerrera, Sébastien Storck, Matthieu Mahévas, Antonio Cosma, Patrick Revy, Thierry Fest, Claude-Agnès Reynaud, Jean-Claude Weill, 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), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Luxembourg Institute of Health (LIH), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
B-Lymphocytes, [SDV]Life Sciences [q-bio], splenic microenvironment, Immunology, affinity selection, [SDV.CAN]Life Sciences [q-bio]/Cancer, Germinal Center, telomeres, smallpox, Infectious Diseases, Immunoglobulin G, memory B cells, Humans, Immunology and Allergy, long-lasting immune memory, Immunologic Memory, vaccinia
Abstract

International audience; Memory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs.

Published
2022
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37. Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals

Author

Noizat-Pirenne F, Annalisa Meola, Claude-Agnès Reynaud, Magali Bouvier-Alias, Laetitia Languille, M. Broketa, Aurélien Sokal, Simon Fillatreau, Jérôme Mégret, Matthieu Mahévas, Anaïs Roeser, Jean-Claude Weill, Alexis Vandenberghe, Bertrand Godeau, Marc Michel, Giovanna Melica, Pascal Chappert, Slim Fourati, Zarrouk, Félix A. Rey, Etienne Crickx, Giovanna Barba-Spaeth, S. Gallien, Imane Azzaoui, Yann Nguyen, Florence Canoui-Poitrine, La Selle Ad, Bruhns P, Jean-Michel Pawlotsky, and Ignacio Fernandez

Subjects
Vaccination, Messenger RNA, Coronavirus disease 2019 (COVID-19), Repertoire, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Potency, Biology, Memory B cell, Neutralization
Abstract

SummaryHow a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.

Published
2021
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39. Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature

Author

Nathalie Costedoat-Chalumeau, St xC phane Durupt, Marc Michel, Arnaud Hot, Bertrand Godeau, Laurent Alric, Lionel Galicier, Zahir Amoura, Matthieu Mahévas, Sophie Alviset, and Hervé Lobbes

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Pure red cell aplasia, Red-Cell Aplasia, Pure, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Pharmacology (medical), Complete response, Therapeutic strategy, Retrospective Studies, 030203 arthritis & rheumatology, biology, Parvovirus, business.industry, Retrospective cohort study, Middle Aged, biology.organism_classification, medicine.disease, Response to treatment, medicine.anatomical_structure, Sustained response, Female, Bone marrow, France, business, Immunosuppressive Agents, 030215 immunology
Abstract

Objectives To characterize the clinical and biological course, management and response to treatment in SLE-associated pure red cell aplasia (PRCA). Methods This was a nationwide, multicentre, retrospective cohort study. From 2006 to 2018, we included adults with a diagnosis of PRCA supported by bone marrow examination and SLE or biologic manifestations of SLE after ruling out parvovirus B19 infection. Results We enrolled 24 patients (20 women). SLE was diagnosed before PRCA for 14 patients (median delay 81 months). At PRCA diagnosis, mean age, haemoglobin level, and reticulocyte and differential erythroblast count were 39.2 (13.2) years, 62 ( 20) g/l, 9.1 (7.6) × 109/l and 2.8 ( 2.5)%, respectively. Eleven (45%) patients experienced multiple PRCA flares (median 6, range 2–11). CS therapy resulted in only three complete sustained responses, and 19 (79%) patients required immunosuppressive agents with highly variable regimens. After a median follow-up of 76 months (range 13–173), 17 (71%) patients showed complete response for PRCA, 5 (21%) partial response and 2 (8%) treatment failure. In total, 21 (87%) patients required red blood cell transfusion; 5 had a diagnosis of transfusion-related iron overload. Eighteen (75%) patients experienced severe infectious events requiring hospitalization. Conclusion SLE-associated PRCA is a severe condition. Repeated red blood cell transfusions and several lines of immunosuppressant therapy are mostly required, with high risk of severe infectious events and iron overload. Despite sustained response for PRCA and SLE obtained in most patients, the best therapeutic strategy remains to be determined.

Published
2021

40. Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data

Author

Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, Sophie Ismaël, Cédric Laouénan, Jennifer Soulier, Oriane Puéchal, Eric D’Ortenzio, Yazdan Yazdanpanah, Laurence Maulin, Stéphanie Martinez, Diane Sanderink, Pascale Fialaire, Séverine Ansart, Lucas Perez, Anne - Laure Destrem, Chloé Moulin, Pascal Gicquel, Frédéric Rivière, Martin Martinot, Mahsa Mohseni Zadeh, Tomasz Chroboczek, Thibaut Challan Belval, Lionel Piroth, Thibault Sixt, Florian Moretto, André Cabié, Jérémie Pasquier, Ornella Cabras, Marine Morrier, Jean Reuter, Thomas Henin, Pierre Braquet, Helene Desmurs-Clavel, Arnaud Hot, Boris Bienvenu, Belkacem Asselate, Nicolas Vignier, Steve Nguala, Sylvain Diamantis, Guillemette Frémont, Pierre Louis Nivose, Mathilde Thiébaut, Benjamin Lefevre, Hélène Auge, Paul le Turnier, Naila Benkalfate, Olivier Grossi, Samuel Pineau, Elisa Demonchy, Julie Merindol, Claire Durand, Nathalie Tieulié, Viviane Queyrel, Didier Laureillard, Paul Loubet, Ségolène Greffe, Nathalie Dournon, Youssouf Mohamed Kassim, Cyrille Gourjault, Alexandre Lahens, Paul Legendre, Caroline Morbieu, Matthieu Mahevas, Giovanna Melica, Jean-Daniel Levièvre, Frédéric Schlemmer, Simone Tunesi, Claire Leblanc, Anne Bourgarit-Durand, Alexandre Bleibtreu, Gianpiero Tebano, Jérôme Pacanowski, Jean-Benoit Zabbe, Mathilde Devaux, Laurent Bellec, Marine Gosset-Woimant, Céleste Lambert, Maxime Hentzien, Amélie Servettaz, Kevin Alexandre, Manuel Etienne, Romain Leguillon, Marion Dollat, Rémi Lefrancois, Anne Pouvaret, Yvon Ruch, Yannick Dieudonné, Guillaume Martin-Blondel, Xavier Boumaza, Margaux Lafaurie, Macha Tetart, Adrien Lemaignen, Nicole Ferreira-Maldent, Amélie Duréault, Marie Gousseff, Claire Chantepie, Francesca Bisio, Fanny Pommeret, Emeline Colomba Blamble, and Claire Ara Somohano

Subjects
0301 basic medicine, Adult, Male, Microbiology (medical), medicine.medical_specialty, Adolescent, medicine.medical_treatment, Therapeutic evaluation, 030106 microbiology, Population, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, Internal medicine, Observational study, Severity of illness, Medicine, Intubation, Corticosteroids, Humans, 030212 general & internal medicine, education, Aged, Mechanical ventilation, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Oxygen Inhalation Therapy, COVID-19, General Medicine, Middle Aged, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Pneumonia, C-Reactive Protein, Infectious Diseases, Original Article, Female, business, medicine.drug
Abstract

OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.

Published
2021
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41. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author

Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

Published
2021
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42. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author

Mickaël M. Ménager, Marine Luka, Marc Michel, Sophie Hue, Slim Fourati, Aurélien Sokal, Simon Fillatreau, Claude-Agnès Reynaud, Giovanna Barba-Spaeth, Annalisa Meola, Laetitia Languille, Jean-Michel Pawlotsky, Matthieu Mahévas, Jérôme Mégret, Félix A. Rey, Etienne Crickx, Asma Beldi-Ferchiou, Magali Bouvier-Alias, Jean-Claude Weill, Imane Azzaoui, Alexis Vandenberghe, Pascal Chappert, Samia Baloul, Anaïs Roeser, Ignacio Fernandez, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Inovarion, Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie, virologie, hygiène [Mondor], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Vaccine Research Institute (VRI), Physiopathologie et immunothérapies dans l’infection VIH [Créteil] (Inserm U955 Équipe 16), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This work was supported by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2), by the Fondation Princesse Grace, and, in part by an ERC Advanced Investigator Grant (B-response). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. A.S. was supported by a Poste d’Accueil from Inserm, A.R. by an Année Recherche from AP-HP and by a SNFMI fellowship., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute [Créteil, France] (VRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Adult, Somatic cell, Cell, Somatic hypermutation, Context (language use), Biology, Lymphocyte Activation, spike protein, Severity of Illness Index, Article, General Biochemistry, Genetics and Molecular Biology, plasma cells, RBD, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, medicine, Humans, neutralizing antibodies, Memory B cell, B cell, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, Germinal center, COVID-19, OC43, Middle Aged, Flow Cytometry, 3. Good health, somatic hypermutation, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, germinal center, Spike Glycoprotein, Coronavirus, Immunology, extrafollicular response, Single-Cell Analysis, HKU1, Immunologic Memory, 030217 neurology & neurosurgery
Abstract

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection., Graphical abstract, The B cell response against SARS-CoV-2 shows a temporal shift from an extrafollicular reaction that includes memory B cells against seasonal coronaviruses toward a germinal center-dependent memory response encoding (spike-specific) neutralizing antibodies.

Published
2021
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43. Thrombopénie immunologique : de la physiopathologie aux traitements

Author

Bernard Bonnotte, Matthieu Mahévas, Sylvain Audia, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Henri Mondor, and CCSD, Accord Elsevier

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Syk, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neonatal Fc receptor, hemic and lymphatic diseases, Internal Medicine, medicine, ComputingMilieux_MISCELLANEOUS, Autoimmune disease, biology, business.industry, Gastroenterology, Autoantibody, medicine.disease, 3. Good health, Immune thrombocytopenia, Treatment, [SDV] Life Sciences [q-bio], 030104 developmental biology, Immunology, biology.protein, Rituximab, Antibody, business, 030215 immunology, medicine.drug
Abstract

International audience; Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an immune peripheral destruction of platelets and an inappropriate platelet production. The pathogenesis of ITP is now better understood: it involves a humoral immune response which dependents on the stimulation of B cells by specific T cells called T follicular helper cells, leading to their differentiation into plasma cells that produce antiplatelet antibodies thus promoting the phagocytosis of platelets mainly by splenic macrophages. The deciphering of ITP pathogenesis has led to a better understanding of the inefficiency of treatments such as rituximab, although it has not provided yet the determination of biological predictive factor of response to treatments. Moreover, new therapeutic perspectives have been opened in the last few years with the development of molecules targeting Fcγ receptor signalling such as Syk inhibitor, or molecules increasing the clearance of pathogenic autoantibodies such as inhibitors of the neonatal Fc receptor (FcRn).

Published
2021
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44. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author

Aurélien Sokal, Pascal Chappert, Anais Roeser, Giovanna Barba-Spaeth, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Ignacio Fernandez, Magali Bouvier-Alias, Etienne Crickx, Asma Beldi Ferchiou, Sophie Hue, Laetitia Languille, Samia Baloul, France Noizat-Pirenne, Marine Luka, Jérôme Megret, Mickaël Ménager, Jean-Michel Pawlotsky, Simon Fillatreau, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, and Matthieu Mahévas

Subjects
medicine.anatomical_structure, Somatic cell, Repertoire, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Cell, Immunology, medicine, Germinal center, Biology, Memory B cell, Gene, B cell
Abstract

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role have been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 Spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including preexisting cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late remarkably stable memory B-cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.

Published
2020
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45. Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

Author

Anne Conrad, Benjamin Wyplosz, Nicolas Benech, Matthieu Mahévas, Bruno Pozzetto, Adrien Lemaignen, Laure Gallay, Dominique Batisse, Rocco Collarino, Dorsaf Slama, Cédric Joseph, Nicolas Vignier, François Goehringer, Elisabeth Botelho-Nevers, Marie Gousseff, Bruno Levy, Pauline Penot, Dominique Salmon, François-Xavier Lescure, Kevin Bouiller, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies infectieuses et tropicales [CHU Amiens], CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Médecine Interne et Maladies Infectieuses [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Henri Mondor [Créteil], Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Henri Mondor, Université Jean Monnet [Saint-Étienne] (UJM), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, MESH: Coronavirus Infections, Disease, 0302 clinical medicine, MESH: Aged, 80 and over, Recurrence, MESH: Reverse Transcriptase Polymerase Chain Reaction, Pandemic, MESH: COVID-19, 030212 general & internal medicine, Young adult, MESH: Aged, MESH: Middle Aged, MESH: Follow-Up Studies, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, MESH: RNA, Viral, MESH: Betacoronavirus, Microbiology (medical), medicine.medical_specialty, MESH: Pandemics, Coronavirus disease 2019 (COVID-19), 030106 microbiology, Article, Viral Relapse, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: SARS-CoV-2, Qatar, MESH: Humans, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, MESH: Recurrence, Pneumonia, MESH: Pneumonia, Viral, Reinfection, Epidemiologic data, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

Published
2020
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46. Association between corticosteroids and intubation or death among patients with COVID-19 pneumonia in non-ICU settings: an observational study using of real-world data from 51 hospitals in France and Luxembourg

Author

Thomas Perpoint, Viet-Thi Tran, François Goehringer, Cocorico, Firouze Bani Sadr, Olivier Robineau, Xavier Lescure, Laure Gallay, Elodie Perrodeau, Philippe Ravaud, and Matthieu Mahévas

Subjects
Mechanical ventilation, medicine.medical_specialty, education.field_of_study, business.industry, medicine.medical_treatment, Mortality rate, Population, medicine.disease, Pneumonia, Prednisone, Internal medicine, Propensity score matching, Medicine, Intubation, Observational study, business, education, medicine.drug
Abstract

ObjectiveTo assess the effectiveness of corticosteroids on outcomes of patients with mild COVID-19 pneumonia.MethodsWe used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) vs standard of care (no-CTC group) among patients ≤ 80 years old with COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death at Day 28. Baseline characteristics of patients were balanced using propensity score inverse probability of treatment weighting.ResultsAmong the 891 patients included in the analysis, 203 were assigned to the CTC group. At day 28, corticosteroids did not reduce the rate of the primary outcome (wHR 0.92, 95% CI 0.61 to 1.39) nor the cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). Corticosteroids significantly reduced the rate of the primary outcome for patients requiring oxygen ≥ at 3L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-Reactive Protein (CRP) ≥ 100mg/L (wHR 0.44, 95%CI 0.23 to 0.85). We found a higher number of hyperglycaemia events among patients who received corticosteroids, but number of infections were similar across the two groups.ConclusionsWe found no association between the use of corticosteroids and intubation or death in the broad population of patients ≤80 years old with COVID-19 hospitalized in non-ICU settings. However, the treatment was beneficial for patients with ≥ 3L/min oxygen or CRP ≥ 100mg/L at baseline. These data support the need to confirm the right timing of corticosteroids for patients with mild COVID.Short summaryWe assessed the effectiveness of corticosteroids among patients ≤ 80 years old with COVID-19, in non-ICU settings. Our results support the use of corticosteroids for patients receiving oxygen at ≥3L/min or with a C-reactive protein ≥ 100mg/L at baseline.

Published
2020
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47. High dose romiplostim as a rescue therapy for adults with severe bleeding and refractory immune thrombocytopenia

Author

Guillaume Moulis, M. Ebbo, M. Hamidou, Virginie Zarrouk, Adrien Chauchet, Mathilde Roumier, François Liferman, Bertrand Lioger, Sébastien Le Burel, Marc Michel, Louis Terriou, Marie Gousseff, Solène Poutrel, Sylvain Audia, Jonathan London, Matthieu Mahévas, Bertrand Godeau, and Lionel Galicier

Subjects
Severe bleeding, Adult, Male, Pediatrics, medicine.medical_specialty, Purpura, Thrombocytopenic, Idiopathic, Romiplostim, Adolescent, business.industry, Recombinant Fusion Proteins, Hemorrhage, Hematology, Receptors, Fc, Middle Aged, Immune thrombocytopenia, Refractory, Thrombopoietin, Rescue therapy, medicine, Humans, Female, business, medicine.drug, Aged
Published
2020

48. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial

Author

null Matthieu Mahévas, null Imane Azzaoui, null Etienne Crickx, null Florence Canoui-Poitrine, null Delphine Gobert, null Laetitia Languille, null Nicolas Limal, null Constance Guillaud, null Laure Croisille, null Mohamed Jeljeli, null Fréderic Batteux, null Samia Baloul, null Olivier Fain, null France Pirenne, null Jean-Claude Weill, null Claude-Agnès Reynaud, null Bertrand Godeau, null Marc Michel, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Etablissement Français du Sang [Île-de-France Mondor], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and AZZAOUI, IMANE

Subjects
Adult, Platelets, medicine.medical_specialty, Combination therapy, [SDV]Life Sciences [q-bio], Immune Thrombocytopenic Purpura, Antibodies, Monoclonal, Humanized, Gastroenterology, Article, Hypogammaglobulinemia, 03 medical and health sciences, Mice, 0302 clinical medicine, immune system diseases, Internal medicine, hemic and lymphatic diseases, Follicular phase, medicine, Clinical endpoint, Animals, Humans, Prospective Studies, Lymphocytes, Adverse effect, 030304 developmental biology, 0303 health sciences, Purpura, Thrombocytopenic, Idiopathic, business.industry, Hematology, medicine.disease, Belimumab, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Cohort, Rituximab, business, 030215 immunology, medicine.drug
Abstract

International audience; B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at one year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single arm, prospective phase 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety.

Published
2020
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49. Acute Hippocampal Encephalopathy in Heavy Cannabis Users: About 2 Cases

Author

Laurent Cleret de Langavant, Armand Mekontso-Dessap, Jérôme Hodel, Constance Lesoil, Alban Gravier, Anne-Catherine Bachoud-Lévi, Matthieu Mahévas, Quang Tuan Rémy Nguyen, Alexandre Bedet, Camille Petit-Hoang, Excitabilité nerveuse et thérapeutique (ENT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, CCSD, Accord Elsevier, and Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Adult, Male, Marijuana Abuse, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Encephalopathy, Hippocampus, Neuropsychological Tests, 030204 cardiovascular system & hematology, Hippocampal formation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Episodic memory, Cannabis, Brain Diseases, biology, medicine.diagnostic_test, business.industry, Electroencephalography, Magnetic resonance imaging, General Medicine, medicine.disease, biology.organism_classification, Magnetic Resonance Imaging, Hippocampal atrophy, 3. Good health, [SDV] Life Sciences [q-bio], business, Rhabdomyolysis
Abstract

Background Cannabis use is increasing worldwide despite the various health effects of this substance. Methods We report 2 cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/d). Results In both male patients, acute encephalitis was suspected. Brain magnetic resonance imaging (MRI) diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis, and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological, and magnetic resonance imaging acute abnormalities improved within weeks. New exposure to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later. Conclusions Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.

Published
2020
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50. Anti-CD20–mediated B-cell depletion in autoimmune diseases: successes, failures and future perspectives

Author

Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas, Etienne Crickx, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, medicine.drug_class, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Disease, Plasma cell, Monoclonal antibody, Lymphocyte Depletion, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Lupus Erythematosus, Systemic, Anti cd20, B cell, B-Lymphocytes, business.industry, Antibodies, Monoclonal, medicine.disease, Antigens, CD20, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, B cell depletion, Nephrology, Immunology, Disease remission, Vasculitis, business, Rituximab
Abstract

B-cell depletion with anti-CD20 monoclonal antibodies is widely used for the treatment of autoimmune diseases. This review will discuss mechanisms contributing to success or failure of B-cell depletion therapy in antibody-mediated autoimmune diseases. It will also explain how key information about disease pathogeny can be provided by the different outcomes observed after B-cell depletion therapy. These findings provide the basis for future innovative therapeutic strategies aiming at an optimized B cell and/or plasma cell depletion to increase long-term disease remission.

Published
2020
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