Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 9, Pages 2132-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.01.031
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Funding
- INSERM
- Normandie University
- French Programme Hospitalier de Recherche Clinique, French Ministry of Health [2008-005266-31]
- French Society of Dermatology
- Region Occitanie/Pyrenees-Mediterranee [1901175]
- European Regional Development Fund [MP0022856]
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The study showed that rituximab significantly decreased DSG-specific memory B cells and eliminated anti-DSG antibody-secreting cells in patients in complete remission. In contrast, corticosteroids did not affect the frequency or phenotype of DSG-specific memory B cells, and anti-DSG antibody-secreting cells were still detected after treatment, even in patients in remission. Additionally, rituximab decreased DSG-specific T follicular helper cells, which remained stable after corticosteroid treatment.
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-3especific 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.
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