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Evolution of autoreactive B and T cells in pemphigus patients with Rituximab or corticosteroid regimen treatment

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Presented at

49th Annual ESDR Meeting

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Abstract

Pemphigus is an autoimmune blistering disease mediated by autoantibodies (Abs) directed against desmogleins (Dsg). We recently showed that first line treatment with Rituximab (RTX) was more effective than standard oral corticosteroid (CS). To understand the immunological mechanisms that mediate the long-lasting clinical remission (CR) after RTX treatment, we analyzed the phenotype and antigen specificity of B cells and T follicular helper cells (TFH) by flow cytometry and the number of Dsg+ IgG Abs Secreting Cell (ASC) by ELISPOT. At Baseline, Dsg+ B cells were detected at a frequency of 0.1-0.6% of total B cells and were enriched in IgG switched memory B cells. Dsg+ IgG ACS were detected at a frequency of 0-0.8% of total ASC for Dsg1 and 0-1.2% for Dsg3. The CS treatment did not influence the frequency nor the phenotype of Dsg+ B cells and Dsg+ ASC, which were detected even in patients in CR. In contrast, RTX induced a significant decrease of IgG switched Dsg+ memory B cells. Accordingly, Dsg+ ASC were no longer detected in patients in CR at M36. Interestingly, Dsg3-specific TFH cells were detected in patients after treatment, with an increased proportion of activated TFH2/TFH17 cell subsets. Strikingly, the frequency of autoreactive TFH cells was much lower in patients treated with RTX than in those treated with CS. Our findings indicate that the response to RTX in pemphigus involves two mechanisms: i) a sustained depletion of IgG switched memory autoreactive B cells leading to the disappearance of Dsg+ ASC, and ii) the decrease of Dsg3-specific circulating TFH cells, which is likely involved in the blockage of B cell maturation and the delayed reappearance of Dsg+ memory B cells.

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© Copyright 2019 Morressier GmbH.
All rights reserved.