B-CELL DEPLETION MODULATES T-HELPER CELL BALANCE IN PATIENTS WITH PRIMARY SJÖGREN'S SYNDROME

Background: 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 the disease process have not been fully elucidated. Alterations in T-helper (Th) cell homeostasis may contribute to the therapeutic effect of RTX in pSS patients as Th cell subset imbalances are involved in the emergence of autoimmune diseases. Objectives: This study assessed the influence of RTX on Th1/Th2/Th17 balance in peripheral blood of pSS patients. Methods: Twenty-eight patients with pSS were treated on days 1 and 15 with RTX (1000 mg i.v.). The frequencies and 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, 48 and 60 weeks after treatment. The expression pattern 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. Sixteen age- and sex-matched healthy individuals were studied in parallel as controls (HCs). Results: At baseline, compared to HCs, pSS patients showed a significant decrease in frequencies and numbers of circulating Th1-cells, and a significant increase in Th17-cells. In contrast, no differences were seen in percentages and numbers of Th2 cells between HCs and pSS patients. Following RTX treatment, frequencies and numbers of Th-cell subsets in pSS patients at 5, 16, and 24 weeks were comparable to pSS baseline values. In contrast, the frequencies and numbers of Th1 cells were significantly increased, whereas frequencies and numbers of Th17 cells were significantly decreased in RTX-patients at 48 and 60 weeks post-treatment, as compared to baseline. Th2 cells remained unchanged at these time points. Importantly, frequencies and numbers of Th1- and Th17 cells in pSS patients at week 60 post-treatment were similar to those in HCs. Conclusions: These data strongly indicate that RTX treatment has profound effects on the distribution of Th cell subsets in pSS patients. Reduction in pro-inflammatory Th17 responses may contribute to the observed clinical outcome of RTX treatment in pSS patients. References: 1. Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial. Meijer JM et al. Arthritis Rheum. 2010 Apr;62(4):960-8. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 71, supplement 3, year 2012, page 315Session: Adaptative immunity (T cells and B cells) in rheumatic diseases (Poster Presentations )