ASSOCIATION OF PATHOGENIC AND REGULATORY B-CELL SUBSETS WITH CLINICAL AND HISTOLOGICAL FEATURES IN PRIMARY SJÖGREN'S SYNDROME

Background: Several data pointed out that B-cells play a central role in the development, maintenance and progression of primary Sjögren's syndrome (pSS). B-lymphocyte hyperactivity, salivary gland (SG) infiltration, and the development of B-cell follicles containing germinal center (GC)-like structures, represent hallmarks of the disease. On this basis, B-cell depleting therapy with anti-CD20 monoclonal antibody rituximab (RTX) has been employed in pSS showing promising results. However, currently available data do not allow to draw definitive conclusion on its efficacy. Objectives: Aim of the study was to assess mature and regulatory B cell subsets in patients with pSS and explore possible associations with clinical and histological features and their possible modulation by RTX treatment. Methods: We evaluated by flow cytometry peripheral blood (PB) B-cell subsets (mature B cells: Bm1, Bm2, Bm2', Bm3, Bm4, early(e)Bm5, Bm5; IL-10-producing B-cells), in 17 pSS patients and in 10 healthy donors (HD). Nine pSS patients received a course of RTX (1000 mg at days 1 and 15) and PB B-cell subsets were also evaluated after 3 (T3) and 6 (T6) months and compared to baseline values (T0). Results: We confirmed that the percentage of Bm1, eBm5 and Bm5 was lower and that of Bm2, Bm2' and Bm3+Bm4 was higher in pSS patients compared to HD (all p<0.05). When we divided patients according to the ESSDAI score (<5 or ≥5) or to SG-GC (presence/absence), we observed for the first time that the percentage of Bm2' cells, also called GC founders, was higher in patients with ESSDAI≥5 (p=0.02) compared to those with lower ESSDAI score and in pSS patients with GC (p=0.02) compared to those without GC. Although we observed a reduction of all B-cells subsets at T3 and T6 after RTX treatment, the proportion of Bm1, Bm3+Bm4, eBm5 and Bm5 persisted lower and the percentage of Bm2 and Bm2' persisted higher in pSS patients (p<0.05) compared to HD. No differences regarding IL-10-producing B-cells was obeserved between pSS patients and HD. However, the percentage of IL-10-producing B-cells was higher in patients with ESSDAI≥5 compared to patients with ESSDAI<5 (p=0.02). Conclusions: We demonstrated for the first time that a subset of circulating mature B-cells, Bm2', also called GC founders, is strongly associated with higher disease activity and with the presence of SG-GC. Moreover, a higher ESSDAI is associated with higher percentage of circulating IL-10-producing B-cells. Pathogenic B-cell hyperactivity is a hallmark of pSS, however B-cells are also a source of inhibitory cytokines such as IL-10 and TGF-beta and the increase of IL-10 producing B cells that we observed in active pSS patients may suggest an ongoing compensatory mechanism to counteract chronic inflammation. Therefore, the design of novel B cell targeted therapies should ensure that only pathogenic B cells are depleted and regulatory B cell subsets are not hampered while, ideally, potentiated. References: Binard A et al. Ann Rheum Dis 2009;68:1447–1452. Carubbi F et al. Arthritis Res Ther 2013;15:R172. Carubbi F et al. Lupus 2014; 23:1337–49. Kroese FG, et al. B-cell hyperactivity in primary Sjögren's syndrome. Expert Rev Clin Immunol. 2014;10:483–99. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2017-eular.4407Citation: Annals of the Rheumatic Diseases, volume 76, supplement 2, year 2017, page 880Session: SLE, Sjögren's and APS - clinical aspects (other than treatment) (Poster Presentations )