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, Vivien Hébert Department of Dermatology, French Reference Center for Auto Immune Blistering Diseases, Rouen University Hospital, Normandie University , Rouen , France Normandie University, UNIROUEN, Inserm, U1234, FOCIS Center of Excellence PAn’THER, Rouen University Hospital, Department of Immunology and Biotherapy , Rouen , France INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM U1291, CNRS U5051, University Toulouse III , Toulouse , France Corresponding author: Vivien Hebert, Email:Vivien.hebert@chu-rouen.fr Search for other works by this author on: Oxford Academic Julien Novarino INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM U1291, CNRS U5051, University Toulouse III , Toulouse , France Search for other works by this author on: Oxford Academic Maud Maho-Vaillant Normandie University, UNIROUEN, Inserm, U1234, FOCIS Center of Excellence PAn’THER, Rouen University Hospital, Department of Immunology and Biotherapy , Rouen , France Search for other works by this author on: Oxford Academic Corine Perals INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM U1291, CNRS U5051, University Toulouse III , Toulouse , France Search for other works by this author on: Oxford Academic Sébastien Calbo Normandie University, UNIROUEN, Inserm, U1234, FOCIS Center of Excellence PAn’THER, Rouen University Hospital, Department of Immunology and Biotherapy , Rouen , France Search for other works by this author on: Oxford Academic Marie-Laure Golinski Normandie University, UNIROUEN, Inserm, U1234, FOCIS Center of Excellence PAn’THER, Rouen University Hospital, Department of Immunology and Biotherapy , Rouen , France Search for other works by this author on: Oxford Academic Fanny Martinez INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM U1291, CNRS U5051, University Toulouse III , Toulouse , France Search for other works by this author on: Oxford Academic Pascal Joly Department of Dermatology, French Reference Center for Auto Immune Blistering Diseases, Rouen University Hospital, Normandie University , Rouen , France Normandie University, UNIROUEN, Inserm, U1234, FOCIS Center of Excellence PAn’THER, Rouen University Hospital, Department of Immunology and Biotherapy , Rouen , France Search for other works by this author on: Oxford Academic Nicolas Fazilleau INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM U1291, CNRS U5051, University Toulouse III , Toulouse , France Search for other works by this author on: Oxford Academic
British Journal of Dermatology, ljae220, https://doi.org/10.1093/bjd/ljae220
Published:
08 June 2024
Article history
Received:
16 May 2023
Revision received:
17 May 2024
Accepted:
06 June 2024
Published:
08 June 2024
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Vivien Hébert, Julien Novarino, Maud Maho-Vaillant, Corine Perals, Sébastien Calbo, Marie-Laure Golinski, Fanny Martinez, Pascal Joly, Nicolas Fazilleau, The emergence of circulating activated autoreactive Dsg3-specific Tfr cells is associated with long-term efficacy of RTX in PV patients, British Journal of Dermatology, 2024;, ljae220, https://doi.org/10.1093/bjd/ljae220
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Abstract
Background
Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocytes adhesion proteins desmoglein (Dsg) 1 and 3, and by the HLA-DRB1-0402 predisposition allele. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission.
Objective
The principal aim of this study is to evaluate the impact of RTX on the circulating subpopulations of Dsg-3-specific T lymphocytes that specifically regulate B cell responses: follicular helper (Tfh) and follicular regulatory T (Tfr) lymphocytes.
Methods
Using the HLA-DRB1-0402 tetramer loaded with the Dsg-3 immunodominant peptide, we analysed by flow cytometry the frequency, the polarisation and the activation status of blood Dsg-3-specific follicular T cell populations at baseline, Month 6 and long-term follow-up (Month 60-90) from PV patients.
Results
At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg-3-specific Tfh cells as compared with non-autoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarisation during patients’ follow-up. In parallel, we observed the emergence of a Dsg-3-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 non-autoreactive Tfr cells of the same PV patients. In contrast, a very few Dsg-3 specific Tfr cells were observed in PV patients treated with CS alone.
Conclusion
Here we show that the emergence of circulating autoreactive Dsg-3-specific Tfr cells is associated with the long-term efficacy of RTX in PV patients.
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