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THU0262 Impaired Suppressive Capacity of Regulatory B Cells in Primary Sjogren's Syndrome

Background primary Sjogren's syndrome (pSS) is a chronic systemic autoimmune disorder that typically affects exocrine glands. B cell hyperactivity is a cardinal feature in pSS[1]. Besides the antibody-producing, regulatory B cells (Breg) has recently been shown to contribute to the maintenance of immunological tolerance[2,3]. The role of the Breg cells in pSS is not well understood. Objectives In this study, we investigated the levels of Breg cells in peripheral blood in patients with pSS, primary biliary cirrhosis (PBC) as well as in healthy controls (HC) and explore the characteristic and function of Breg cells in pSS patients. Methods Newly diagnosed pSS patients (n=70) were enrolled, 50 healthy volunteers and 25 PBC patients were recruited as healthy and disease controls. To analyze the percentages of Breg cells and the level of IL-10 secreted by Breg cells, PBMCs were surface and intracellular stained, and detected by flow cytometry. The expression of IL-10 in B cells were determined by real-time PCR. The function of Breg cells was tested by co-culturing isolated CD19+CD24hiCD38hi Breg cells with purified CD4+CD25–T cells (Teff cells) from pSS patients or HC at a ratio of 1:1. The cytokines in culture supernatants were measured by cytometric beads array. Results The frequency of circulating Breg cells in pSS patients was significantly increased, compared with PBC patients and HC (6.88 ± 2.48%, 1.95 ± 1.04%, and 1.52±0.65%, respectively; p<0.0001). The percentages of IL-10+ Breg cells was much lower in pSS patients, compared to PBC and HC (16.04 ± 9.03%, 81.40 ± 21.00%, 31.00 ± 7.79%, respectively; p<0.05), while the expression of IL-10 in B cells was much higher in pSS patients than that in HC (13.48 ± 18.90, 3.55 ± 0.71, respectively; p<0.05). When autologous or heterologous Teff cells/ Breg cells were co-cultured, IFN-γ, TNF-α, IL-4, IL-17 in supernatants secreted by HC or pSS Teff cells significantly suppressed by healthy Breg cells, not by Breg cells in pSS patients (p<0.05). Conclusions This preliminary study showed that the frequency of Breg cells was significantly increased in pSS patients. Although the expresssion of IL-10 mRNA in B cells was much higher, the secretion of IL-10 of Breg cells from pSS patients was decreased and less effective in the control of Teff cell proliferation. Unlike HC, the suppressive capacity of Breg cells was impaired in pSS. The malfunctioning Breg cells may play an important role in pathogenesis of pSS. References Nocturne G, Mariette X. Advances in understanding the pathogenesis of primary Sjogren's syndrome. Nat Rev Rheumatol 2013;9:544–56. Blair PA, Norena LY, Flores-Borja F, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 2010;32:129–40. Lund FE, Randall TD. Effector and regulatory B cells: modulators of CD4+ T cell immunity. Nat Rev Immunol 2010;10:236–47. Disclosure of Interest None declared