1. The emergence of circulating activated autoreactive desmoglein 3-specific follicular regulatory T cells is associated with long-term efficacy of rituximab in patients with pemphigus vulgaris.
- Author
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Hébert V, Novarino J, Maho-Vaillant M, Perals C, Calbo S, Golinski ML, Martinez F, Joly P, and Fazilleau N
- Subjects
- Humans, Male, Female, Middle Aged, Treatment Outcome, Adult, Aged, Immunologic Factors, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer drug effects, HLA-DRB1 Chains genetics, HLA-DRB1 Chains immunology, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Pemphigus immunology, Pemphigus drug therapy, Pemphigus blood, Desmoglein 3 immunology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory drug effects, Rituximab therapeutic use, Rituximab pharmacology, Autoantibodies immunology, Autoantibodies blood
- Abstract
Background: Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocyte adhesion proteins desmoglein (Dsg) 1 and 3, and by the human leukocyte antigen (HLA) predisposition allele HLA-DRB1*0402. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission., Objectives: The principal aim of this study was to evaluate the impact of RTX on the circulating subpopulations of Dsg3-specific T lymphocytes that specifically regulate B-cell responses: follicular helper T (Tfh) and follicular regulatory T (Tfr) lymphocytes., Methods: Using the HLA-DRB1*0402 tetramer loaded with the Dsg3 immunodominant peptide, we used flow cytometry to analyse the frequency, polarization and activation status of blood Dsg3-specific follicular T-cell populations at baseline, month (M) 6 and long-term follow-up (M60-90) from patients with PV., Results: At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg3-specific Tfh cells compared with nonautoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarization during follow-up. In parallel, we observed the emergence of a Dsg3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS and CD25 that was not observed at the surface of autoreactive Tfh and nonautoreactive Tfr cells of the same patients with PV. In contrast, very few Dsg3-specific Tfr cells were observed in patients with PV who were treated with CS alone., Conclusions: Here we show that the emergence of circulating autoreactive Dsg3-specific Tfr cells is associated with the long-term efficacy of RTX in patients with PV., Competing Interests: Conflicts of interest V.H. reports administrative support was provided by the French Society for Dermatology and Pathology of Sexually Transmitted Diseases. P.J. reports a relationship with Roche SAS that includes board membership. N.F. reports financial support provided by the European Regional Development Fund, the French Society for Dermatology and Pathology of Sexually Transmitted Diseases, the National Institute of Health and Medical Research, the Agence Nationale de la Recherche (ANR) and the Occitanie Region., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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