Abstract
IntroductionWe aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA). Patients and methodsWe analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4+IL23R+IL17A+) and Treg cells (CD4+CD25hiFoxP3+) were evaluated flow-cytometrically. ResultsTh17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4+ cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (−) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033). ConclusionRTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (−) patients with RA.
Highlights
We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA)
Since different cells of the immune system are inter-related via a multitude of pathways and mechanisms, we asked the question of whether B cell depletion treatment potentially alters T cells as well in patients with RA
In some (n = 6) patients with RA initiating treatment with RTX we evaluated for potential changes of a subpopulation of surface Th17-expressing T cells, which express IL-17A on their surface membrane following ex vivo stimulation with phorbol myristate acetate (PMA) and ionomycin as described above
Summary
We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA). The aim of this study was to investigate if treatment of patients with RA with RTX could induce any changes in the numbers of peripheral Treg and Th17 cells. To address this question, we analyzed flow-cytometrically circulating T cell subpopulations before and after treatment with RTX at defined time points. Our experimental data suggest that B cell depletion in patients with RA significantly reduces peripheral Th17 cells whereas numbers of Tregs remain unaffected
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