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Rituximab and Corticosteroid Effect on Desmoglein-Specific B Cells and Desmoglein-Specific T Follicular Helper Cells in Pemphigus.
Maho-Vaillant, Maud; Perals, Corine; Golinski, Marie-Laure; Hébert, Vivien; Caillot, Frédérique; Mignard, Claire; Riou, Gaëtan; Petit, Marie; Viguier, Manuelle; Hertl, Michael; Boyer, Olivier; Calbo, Sébastien; Fazilleau, Nicolas; Joly, Pascal.
Afiliação
  • Maho-Vaillant M; Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Auto-Immunes, Normandie University, Rouen, France; INSERM U1234, UNIROUEN, Normandie University, Rouen, France. Electronic address: maud.maho@univ-rouen.fr.
  • Perals C; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM U1291, CNRS U5051, University of Toulouse, Toulouse, France.
  • Golinski ML; Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Auto-Immunes, Normandie University, Rouen, France; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Hébert V; Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Auto-Immunes, Normandie University, Rouen, France; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Caillot F; Department of Biostatistics, Rouen University Hospital, Rouen, France.
  • Mignard C; Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Auto-Immunes, Normandie University, Rouen, France.
  • Riou G; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Petit M; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Viguier M; Department of Dermatology, Centre de Référence des Maladies Bulleuses Auto-Immunes and EA 7509, Reims-Champagne Ardenne University, Reims, France.
  • Hertl M; Department of Dermatology and Allergology, Philipps University, Marburg, Germany.
  • Boyer O; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Calbo S; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
  • Fazilleau N; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM U1291, CNRS U5051, University of Toulouse, Toulouse, France.
  • Joly P; Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Auto-Immunes, Normandie University, Rouen, France; INSERM U1234, UNIROUEN, Normandie University, Rouen, France.
J Invest Dermatol ; 141(9): 2132-2140.e1, 2021 09.
Article em En | MEDLINE | ID: mdl-33766510
Pemphigus is an autoimmune blistering disease mediated by autoantibodies directed against desmogleins (DSGs). We recently showed that first-line treatment with rituximab (RTX) enables more patients to achieve long-lasting remission off therapy than corticosteroids alone. To understand the immunological mechanisms that mediate long-lasting clinical remission after RTX treatment, we analyzed the phenotype of DSG-specific memory B cells and DSG-specific T follicular helper cells by flow cytometry and measured antibody-secreting cells by enzyme-linked immune absorbent spot in patients treated with corticosteroids alone or RTX. This post hoc analysis of the RITUX3 trial showed that RTX induced a significant decrease of IgG-switched DSG-specific memory B cells. Accordingly, anti-DSG antibody-secreting cells were no longer detected in patients in complete remission after RTX. In contrast, corticosteroids did not modify the frequency or the phenotype of DSG-specific memory B cells, and anti-DSG antibody-secreting cells were still detected after treatment, even in patients in remission. Using peptide-HLADRB1∗0402 tetramer staining, we identified DSG-3-specific T follicular helper cells, which dramatically decreased after RTX, while remaining stable after corticosteroid treatment. Our findings suggest that long-lasting response to RTX in pemphigus relies on the decrease of DSG-specific circulating T follicular helper cells, which correlates with a sustained depletion of IgG-switched memory autoreactive B cells, leading to the disappearance of anti-DSG antibody-secreting cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subpopulações de Linfócitos B / Pênfigo / Corticosteroides / Linfócitos T Auxiliares-Indutores / Centro Germinativo / Rituximab / Imunossupressores Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subpopulações de Linfócitos B / Pênfigo / Corticosteroides / Linfócitos T Auxiliares-Indutores / Centro Germinativo / Rituximab / Imunossupressores Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article