Session Title: Sjögren's Syndrome: Clinical Advances
Session Type: Abstract Submissions (ACR)
B-cell depletion therapy with a chimeric anti-human CD20 antibody (rituximab; RTX) is an effective treatment modality for patients with primary Sjögren’s syndrome (pSS). However, the mechanisms through which RTX exerts its effects on pSS have not been fully elucidated. Alterations in T-helper (Th) cell homeostasis may contribute to the therapeutic effect of RTX as Th cell subset imbalances are involved in the emergence of autoimmune diseases. The current study assessed the influence of RTX on Th1/Th2/Th17 balance in peripheral blood of pSS patients.
Twenty-eight patients with pSS, diagnosed according to the American-European Consensus Group criteria, were treated on days 1 and 15 with RTX (1000 mg i.v.). The absolute numbers of circulating Th1/Th2/Th17 cell subsets were examined in fresh blood samples by 6-color flow cytometry at baseline and at 5, 16, 24 and 36 weeks after treatment. Expression patterns of chemokine receptors CXCR3+CRTh2–CCR4–CCR6–, CXCR3–CRTh2+CCR4+CCR6– and CXCR3–CRTh2–CCR4+CCR6+ were used for distinction between Th1, Th2 and Th17, respectively. In addition, numbers of Th1/Th2/Th17 cells were analyzed based on their associated cytokines IFNg/IL-4/IL-17 upon in vitro stimulation of thawed PBMCs. Sixteen matched healthy individuals were studied in parallel as controls (HCs).
At baseline, compared to HCs, pSS patients showed a significant decrease in numbers of circulating Th1-cells, and a significant increase in Th17-cells. In contrast, no differences were seen in numbers of Th2 cells between HCs and pSS patients. Following RTX treatment, numbers of circulating Th1 and Th2 subsets in pSS patients at 5, 16 and 24 weeks were comparable to their baseline values, whereas a significant decrease was observed in Th17 cells at week 5 post-treatment. Importantly, RTX treatment induced a significant decrease in number of IL-17 producing Th-cells at weeks 16 and 24 as compared to baseline, whereas IFNg and IL-4 producing Th-cells remained unchanged. Importantly, numbers of IL-17 producing Th-cells increased again and reached their baseline value by 36 weeks post RTX-treatment. This coincides with a reconstitution of B cells in peripheral blood of pSS patients.
B cell depletion therapy in pSS influences Th cell homeostasis affecting Th17 cells in particular. Recovery of Th17 cells coincides with B cell repopulation indicates that B cells modulate the pro-inflammatory Th17 responses. Reduction in Th17 responses post RTX-treatment may contribute to the observed clinical outcome of RTX in pSS patients.
P. Meiners, BMS, 2; A. Vissink,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-depletion-modulates-t-helper-cell-balance-in-patients-with-primary-sjogrens-syndrome/