Research Topics

• Myositis
• Autoimmune bullous diseases
• Pathogenic B cells
• Immunotherapy, Advanced Therapy Medicinal Products (ATMP)

  Composition

• 39 scientists, professors, engineers, technicians
• 9 PhD students

  Facilities

• Flow cytometry core facility (FACSorting and single-cell analysis)
• Clinical cell/gene therapy facility (in collaboration with Rouen University Hospital)
• Virus-mediated gene transfer
• In vivo experimental models
• Development of immunoassays

  Activity

The research program of Inserm U1234 focuses on the cellular and molecular pathophysiological mechanisms involved in the onset and progression of myositis and autoimmune bullous cutaneous diseases. In these two clinical contexts and some related diseases such as rheumatoid arthritis, we aim at delineating the pathogenic roles of autoreactive B cells and autoantibodies (aAbs). This is done through both (i) experimental studies based on animal immunization or autoantibody/cell transfer, as well as spontaneous autoimmune animal models or new models under development and, (ii) translational studies with in-depth characterization of human autoreactive B cell responses at the bulk and single cell level and structural/functional features of aAbs isolated from patients. On the therapeutic side, we design new therapeutic tools for immunointervention in cancer and autoimmunity including cell/gene therapy (lentiviral vectors and AAV, CAR/CAAR-T cells, nanobodies). These immunotherapies are evaluated in experimental models of myositis, bullous diseases and cancer. Thanks to our close collaboration with clinical departments and ATMP facility of Rouen University Hospital, we conduct or participate in several immunotherapy clinical trials.

The work of Inserm U1234 in the field of myositis, autoimmune bullous diseases and T-cell immunotherapy is the core research project of the PAn’THER Center of Excellence (Director O. Boyer, deputy director C. Abad) of the US-based Federation of Clinical Immunology Societies. https://irib.univ-rouen.fr/focis.php

  Main contributions

• Evaluation and detailed immune-monitoring of B cell targeted therapies that changed the therapeutic strategies in autoimmune bullous diseases.
• Demonstration of the pathogenic role of autoantibodies (anti-SRP, anti-HMGCR) in immune-mediated necrotizing myopathies.
• Discovery of biomarkers associated to cancer (tumor somatic mutations, anti-TIF1γ autoantibody levels and isotypes) in dermatomyositis
• First randomized placebo-controlled ATMP clinical trial demonstrating efficacy of myoblast therapy in sphincter insufficiency.

  Latest publications

2021

• Bertrand D, Hamzaoui M, Lemée V, Lamulle J, Hanoy M, Laurent C, Lebourg L, Etienne I, Lemoine M, Le Roy F, Nezam D, Plantier JC, Boyer O, Guerrot D and Candon S. Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis Patients. J Am Soc Nephrol 2021, 32(9): 2147-2152.
  34112706
• Joly P, Tejedor I, Tetart F, Cailleux HC, Barrel A, De Preville PA, Mion-Mouton N, Gabison G, Baricault S, Tordeur CG, Dore MX, Rossi B, Bourseau-Quetier C, Chamaillard M, Ly S, Chosidow O, Richard-Lallemand MA, Rzeznik JC, Amici JM, Lair G, Bechu S, Benichou J, Thill C and Beylot-Barry M. Tacrolimus 0.1% versus ciclopiroxolamine 1% for maintenance therapy in patients with severe facial seborrheic dermatitis: A multicenter, double-blind, randomized controlled study. J Am Acad Dermatol 2021, 84(5): 1278-1284.
  33010323
• Maho-Vaillant M, Perals C, Golinski ML, Hébert V, Caillot F, Mignard C, Riou G, Petit M, Viguier M, Hertl M, Boyer O, Calbo S, Fazilleau N and Joly P. Rituximab and Corticosteroid Effect on Desmoglein-Specific B Cells and Desmoglein-Specific T Follicular Helper Cells in Pemphigus. J Invest Dermatol 2021, 141(9): 2132-2140.e1.
  33766510

2020

• Allenbach Y, Benveniste O, Stenzel W and Boyer O. Immune-mediated necrotizing myopathy: clinical features and pathogenesis. Nat Rev Rheumatol 2020, 16(12): 689-701.
  33093664
• Hébert V, Duval-Modeste AB, Joly P, Lemée V, Cellier L, Jouen F, Veber B, Drouot L and Boyer O. Lack of association between chilblains outbreak and severe acute respiratory syndrome coronavirus 2: Histologic and serologic findings from a new immunoassay. J Am Acad Dermatol 2020, 83(5): 1434-1436.
  32682889
• Mignard C, Maho-Vaillant M, Golinski ML, Balayé P, Prost-Squarcioni C, Houivet E, Calbo SB, Labeille B, Picard-Dahan C, Konstantinou MP, Chaby G, Richard MA, Bouaziz JD, Duvert-Lehembre S, Delaporte E, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D', Incan M, Bédane C, Bénéton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Benichou J, Joly P, Hébert V and . Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Dermatol 2020, 156(5): 545-552.
  32186656

2019

• Aussy A, Fréret M, Gallay L, Bessis D, Vincent T, Jullien D, Drouot L, Jouen F, Joly P, Marie I, Meyer A, Sibilia J, Bader-Meunier B, Hachulla E, Hamidou M, Huë S, Charuel JL, Fabien N, Viailly PJ, Allenbach Y, Benveniste O, Cordel N, Boyer O and . The IgG2 Isotype of Anti-Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis. Arthritis Rheumatol 2019, 71(8): 1360-1370.
  30896088
• Bergua C, Chiavelli H, Allenbach Y, Arouche-Delaperche L, Arnoult C, Bourdenet G, Jean L, Zoubairi R, Guerout N, Mahler M, Benveniste O, Drouot L and Boyer O. In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. Ann Rheum Dis 2019, 78(1): 131-139.
  30309969
• Koch-Nolte F, Eichhoff A, Pinto-Espinoza C, Schwarz N, Schäfer T, Menzel S, Haag F, Demeules M, Gondé H and Adriouch S. Novel biologics targeting the P2X7 ion channel. Curr Opin Pharmacol 2019, 47: 110-118.
  30986625

2018

• Boyer O, Bridoux V, Giverne C, Bisson A, Koning E, Leroi AM, Chambon P, Déhayes J, Le Corre S, Jacquot S, Bastit D, Martinet J, Houivet E, Tuech JJ, Benichou J and Michot F; and the Study Group of Myoblast Therapy for Faecal Incontinence. Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). Ann Surg 2018
  28426476
• Plaquevent M, Tétart F, Fardet L, Ingen-Housz-Oro S, Valeyrie-Allanore L, Bernard P, Hebert V, Roussel A, Avenel-Audran M, Chaby G, D', Incan M, Ferrier-Le-Bouedec MC, Duvert-Lehembre S, Picard-Dahan C, Jeudy G, Collet E, Labeille B, Morice C, Richard MA, Bourgault-Villada I, Litrowski N, Bara C, Mahe E, Prost-Squarcioni C, Alexandre M, Quereux G, Bernier C, Soria A, Thomas-Beaulieu D, Pauwels C, Dereure O, Benichou J, Joly P, and . Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population. J Invest Dermatol 2018, 139(4): 835-841.
  30543900

2017

• Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard MA, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Bénéton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J and Musette P; French study group on autoimmune bullous skin diseases. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017, 389: 2031-2040.
  28342637

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