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from basic science:
to the translational research:
Matthieu Mahevas

Matthieu Mahévas is a physician-researcher in the French reference center for immune thrombocytopenia at Henri-Mondor Hospital (CERECAI). He did his PhD in the lab of Claude-Agnès Reynaud and Jean-Claude Weill at Institut Necker-Enfants Malades (INEM), during which he demonstrated that B cell-depletion therapy favors the emergence of splenic long-lived pathogenic plasma cells. Named MCU-PH in 2014 and PU-PH at the Faculté de Médecine de l’Université Paris-Est Créteil in 2019, he has been awarded an ATIP/Avenir grant in 2022 and is since 2023 the head of the group “Auto-immune and immune B cells (AI2B)” at Institut Necker Enfants Malades where he pursues is early clinical and scientific research interests focused on understanding the cellular and molecular mechanisms of auto-immune disease and on developing innovative therapies, with numerous past and ongoing clinical trials (RITUX-PLUS, RITUX-PLUS2, IVIORDEX, STOPAGO). More recently, his group also used its unique expertise at studying human B cells at the single cell level to provide seminal work on the maturation of memory B cells after SARS-CoV-2 infection or mRNA vaccination. He has been elected as a fellow of the Henri Kunkel Society in 2021.

2023

  • Sokal A, Bastard P, Chappert P, Barba-Spaeth G, Fourati S, Vanderberghe A, Lagouge-Roussey P, Meyts I, Gervais A, Bouvier-Alias M, Azzaoui I, Fernández I, de la Selle A, Zhang Q, Bizien L, Pellier I, Linglart A, Rothenbuhler A, Marcoux E, Anxionnat R, Cheikh N, Léger J, Amador-Borrero B, Fouyssac F, Menut V, Goffard JC, Storey C, Demily C, Mallebranche C, Troya J, Pujol A, Zins M, Tiberghien P, Gray PE, McNaughton P, Sullivan A, Peake J, Levy R, Languille L, Rodiguez-Gallego C, Boisson B, Gallien S, Neven B, Michel M, Godeau B, Abel L, Rey FA, Weill JC, Reynaud CA, Tangye SG, Casanova JL, Mahévas M.
    Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination.
    J Exp Med. 2023 Jan 2;220(1):e20220258. doi: 10.1084/jem.20220258. Epub 2022 Nov 7.
  • 2022

  • Chappert P, Huetz F, Espinasse MA, Chatonnet F, Pannetier L, Da Silva L, Goetz C, Mégret J, Sokal A, Crickx E, Nemazanyy I, Jung V, Guerrera C, Storck S, Mahévas M, Cosma A, Revy P, Fest T, Reynaud CA, Weill JC.
    Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting.
    Immunity. 2022 Oct 11;55(10):1872-1890.e9. doi: 10.1016/j.immuni.2022.08.019. Epub 2022 Sep 20.
  • Attias P, Azzaoui I, El Karoui K, de La Selle A, Sokal A, Chappert P, Grimbert P, Fernandez I, Bouvier M, Samson C, Dahmane D, Rieu P, Nizard P, Fourati S, Sakhi H, Mahévas M; Mondor NephroCov Study Group.
    Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2- Recovered Dialysis Patients.
    Clin J Am Soc Nephrol. 2022 Jul;17(7):1008-1016. doi: 10.2215/CJN.00830122. Epub 2022 Jun 28.
  • Sokal A, Broketa M, Barba-Spaeth G, Meola A, Fernández I, Fourati S, Azzaoui I, de La Selle A, Vandenberghe A, Roeser A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Noizat-Pirenne F, Megret J, Pawlotsky JM, Fillatreau S, Simon-Lorière E, Weill JC, Reynaud CA, Rey FA, Bruhns P, Chappert P, Mahévas M.
    Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant.
    Immunity. 2022 Jun 14;55(6):1096-1104.e4. doi: 10.1016/j.immuni.2022.04.002. Epub 2022 Apr 7.
  • 2021

  • Sokal A, Barba-Spaeth G, Fernández I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Pirenne F, Mégret J, Pawlotsky JM, Fillatreau S, Bruhns P, Rey FA, Weill JC, Reynaud CA, Chappert P, Mahévas M.
    mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants.
    Immunity 2021 Sep 21:S1074-7613(21)00396-4.
  • Crickx E, Chappert P, Sokal A, Weller S, Azzaoui I, Vandenberghe A, Bonnard G, Rossi G, Fadeev T, Storck S, Fadlallah J, Meignin V, Rivière E, Audia S, Godeau B, Michel M, Weill JC, Reynaud CA. Mahévas M.
    Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia.
    Science Translational Medicine 2021. 14 avr 2021;13(589).
  • Reynaud CA, Weill JC, Chappert P, Mahévas M.
    Des anticorps contre l’infection initiale et des lymphocytes B à mémoire contre les infections futures.
    Med Sci (Paris). 2021 Aug-Sep;37(8-9):722-725.
  • Sokal A, Chappert P, Barba-Spaeth G, Roeser A, Fourati S, Azzaoui I, Vandenberghe A, Fernandez I, Meola A, Bouvier-Alias M, Crickx E, Beldi-Ferchiou A, Hue S, Languille L, Michel M, Baloul S, Noizat-Pirenne F, Luka M, Mégret J, Ménager M, Pawlotsky JM, Fillatreau S, Rey FA, Weill JC, Reynaud CA, Mahévas M.
    Maturation and persistence of the anti-SARS-CoV-2 memory B cell response.
    Cell. 2021 Feb 2:S0092-8674(21)00093-3.
  • 2020

  • Mahévas M, Azzaoui I, Crickx E, Canoui-Poitrine F, Gobert D, Languille L, Limal N, Guillaud C, Croisille L, Jeljeli M, Batteux F, Baloul S, Fain O, Pirenne F, Weill JC, Reynaud CA, Godeau B, Michel M.
    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.
    Haematologica. 2020 Aug 13.
  • 2018

  • Thai LH, Le Gallou S, Robbins A, Crickx E, Fadeev T, Zhou Z, Cagnard N, Mégret J, Bole C, Weill JC, Reynaud CA, Mahévas M.br/> BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell-depletion context.
    Blood. 2018 Apr 5;131(14):1545-1555.
  • Chadebech P, Loustau V, Janvier D, Languille L, Ripa J, Tamagne M, Bierling P, Djoudi R, Godeau B, Michel M, Pirenne F, Mahévas M.
    Clinical severity in adult warm autoimmune hemolytic anemia and its relationship to antibody specificity.
    Haematologica. 2018 Jan;103(1):e35-e38.
  • <= 2017

  • Mahévas M, Gerfaud-Valentin M, Moulis G, Terriou L, Audia S, Guenin S, Le Guenno G, Salles G, Lambotte O, Limal N, Viallard JF, Cheze S, Tomowiak C, Royer B, Neel A, Debouverie O, Hot A, Durieu I, Perlat A, Cliquennois M, Deteix C, Michel M, Godeau B.
    Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia.
    Blood. 2016 Sep 22;128(12):1625-30.
  • Mahévas M, Michel M, Vingert B, Moroch J, Boutboul D, Audia S, Cagnard N, Ripa J, Menard C, Tarte K, Mégret J, Le Gallou S, Patin P, Thai L, Galicier L, Bonnotte B, Godeau B, Noizat-Pirenne F, Weill JC, Reynaud CA.
    Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.
    J Autoimmun. 2015 Aug;62:22-30.
  • Mahévas M, Patin P, Descatoire M, Huetz F, Cagnard N, Le Gallou S, Hamidou M, Khellaf M, Fain O, Fieschi C, Galicier L, Schleinitz N, Lambotte O, Bierling P, Michel M, Godeau B, Reynaud C and Weill JC.
    B-cell depletion in immune thrombocytopenia revealed splenic long lived plasma cells.
    J Clin Invest. 2013 Jan 2;123(1):432-42.
  • Autoimmune and immune B cells (AI2B)

    Focus

    Our group investigates the underlying mechanisms, cellular populations involved and fundamental steps leading to the tolerance breakdown in B cells and the establishment of a long-lived immune memory in normal and pathologic context in Human.

    Introduction

    Both plasma cells and long-lived memory B cells have been shown to participate in long-term protection against pathogens. And the most effective vaccines can induce a lifelong memory response in immunized individuals, as is the case with smallpox or yellow fever vaccination.

    However, B cells and plasma cells targeting self-antigens have also been highlighted as key players in the development of numerous autoimmune diseases, including immune thrombocytopenia (ITP), or severe form of COVID-19. Our laboratory focuses on two central questions in immunology:

    1. Why do some individuals develop auto-immune disorders?
    2. How, and when, do we keep memory B for decades and what is the relationships between long-lived memory B cell and plasma cell generation in Human?

    Research objectives

    Our first objective in the lab aims at addressing the fundamental question of tolerance breakdown in Human from two independent angles. Using first a unique access to splenic samples from immune thrombocytopenia (ITP) patients at different stage in the disease and with likely different etiologies, we aim to draw upon our previous work in ITP, a prototypical B cell mediated auto-immune disease, to explore the underlying cause(s) of tolerance breakdown in B cells and define the pathogenic program of auto-immune plasma cells, key actors of the auto-immune response. In parallel to this, our group is also part of a national consortium (RHU COFIFERON) aiming in part at better understanding the origin of anti-Type I IFN antibodies in older adults, auto-antibodies notably at the basis of severe forms of COVID-19.

    A second major focus in the lab has been to decipher the cellular mechanisms involved in memory B cell generation and longevity. The SARS-CoV-2 pandemic and the subsequent worldwide vaccination campaign has provided us with a perfect physiological “model” to describe the early steps of a response to a neo-viral antigen in human. We also recently took advantage of the unique setting provided by smallpox eradication in the late 1970s to perform the first functional analysis of 50 years old resting memory B cells in Human. We are now building upon these works to 1) decipher the role of antigen imprinting in shaping B cell memory to drifted SARS-CoV2 variants both in the context of breakthrough infections or variant-based vaccine development, 2) address the separate question of the functional longevity of such response through the analysis of SARS-CoV-2-specific memory B cells and plasma cells seeding in known niches of long-lasting immune cells as well as through the analysis of the recruitment of decades old vaccinia-generated memory B cells in the recent Monkeypox outbreak and subsequent MVA vaccination campaign.

    5 main publications

    • Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination.
      Sokal A, Bastard P, Chappert P, Barba-Spaeth G, Fourati S, Vanderberghe A, Lagouge-Roussey P, Meyts I, Gervais A, Bouvier-Alias M, Azzaoui I, Fernández I, de la Selle A, Zhang Q, Bizien L, Pellier I, Linglart A, Rothenbuhler A, Marcoux E, Anxionnat R, Cheikh N, Léger J, Amador-Borrero B, Fouyssac F, Menut V, Goffard JC, Storey C, Demily C, Mallebranche C, Troya J, Pujol A, Zins M, Tiberghien P, Gray PE, McNaughton P, Sullivan A, Peake J, Levy R, Languille L, Rodiguez-Gallego C, Boisson B, Gallien S, Neven B, Michel M, Godeau B, Abel L, Rey FA, Weill JC, Reynaud CA, Tangye SG, Casanova JL, Mahévas M.
      J Exp Med. 2023 Jan 2;220(1):e20220258. doi: 10.1084/jem.20220258.
    • Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting.
      Chappert P, Huetz F, Espinasse MA, Chatonnet F, Pannetier L, Da Silva L, Goetz C, Mégret J, Sokal A, Crickx E, Nemazanyy I, Jung V, Guerrera C, Storck S, Mahévas M, Cosma A, Revy P, Fest T, Reynaud CA, Weill JC.
      Immunity. 2022 Oct 11;55(10):1872-1890.e9. doi: 10.1016/j.immuni.2022.08.019.
    • mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants.
      Sokal A, Barba-Spaeth G, Fernández I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Pirenne F, Mégret J, Pawlotsky JM, Fillatreau S, Bruhns P, Rey FA, Weill JC, Reynaud CA, Chappert P, Mahévas M.
      Immunity. 2021 Dec 14;54(12):2893-2907.e5. doi: 10.1016/j.immuni.2021.09.011.
    • Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia.
      Crickx E, Chappert P, Sokal A, Weller S, Azzaoui I, Vandenberghe A, Bonnard G, Rossi G, Fadeev T, Storck S, Fadlallah J, Meignin V, Rivière E, Audia S, Godeau B, Michel M, Weill JC, Reynaud CA. Mahévas M.
      Science Translational Medicine 2021. 14 avr 2021;13(589).
    • Maturation and persistence of the anti-SARS-CoV-2 memory B cell response.
      Sokal A, Chappert P, Barba-Spaeth G, Roeser A, Fourati S, Azzaoui I, Vandenberghe A, Fernandez I, Meola A, Bouvier-Alias M, Crickx E, Beldi-Ferchiou A, Hue S, Languille L, Michel M, Baloul S, Noizat-Pirenne F, Luka M, Mégret J, Ménager M, Pawlotsky JM, Fillatreau S, Rey FA, Weill JC, Reynaud CA, Mahévas M.
      Cell. 2021 Feb 2:S0092-8674(21)00093-3.
    Permanent researcher
    Pascal Chappert
    Researcher
    +33 (0)1 40 61 54 17
    Matthieu Mahevas
    Professor Researcher
    +33 (0)1 40 61 54 17
    Claude-Agnès Reynaud
    -
    +33 (0)1 40 61 54 17
    Jean-Claude Weill
    -
    +33 (0)1 40 61 54 18
    Non permanent researcher
    Aurélien Sokal
    Clinician
    +33 (0)1 40 61 54 17
    Permanent engineer
    Alexis Vanderberghe
    -
    +33 (0)1 40 61 54 21
    Non permanent engineer
    Pauline Lagouge-Roussey
    Engineer
    +33 (0)1 40 61 54 21
    Post-doctoral degree
    Manon Broutin
    Post-Doctoral Researcher
    +33 (0)1 40 61 54 21
    Matthias Vanderkerken
    Post-Doctoral Researcher
    +33 (0)1 40 61 54 21
    PhD
    Clara Cousu
    PhD Student
    +33 (0)1 40 61 54 21
    Anais Roeser
    PhD Student
    +33 (0)1 40 61 54 21
    Student
    Pierre Louis Cariou
    Graduate student
    +33 (0)1 40 61 54 21
    Paolo Van Endert
    Graduate student
    +33 (0)1 40 61 54 21
    Address

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    Support(s)
    HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

    INEM - Organigramme