SAT0284 Association of pathogenic and regulatory B-cell subsets with clinical and histological features in primary sjÖgren's syndrome
Authors: F Carubbi, A Alunno, P Cipriani, P Di Benedetto, V Liakouli, P Ruscitti, O Berardicurti, S Di Bartolomeo, R Gerli, R Giacomelli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several data pointed out that B-cells play a central role in the development, maintenance and progression of primary Sjögren9s 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. <h3>Objectives</h3> 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. <h3>Methods</h3> We evaluated by flow cytometry peripheral blood (PB) B-cell subsets (mature B cells: Bm1, Bm2, Bm29, 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). <h3>Results</h3> We confirmed that the percentage of Bm1, eBm5 and Bm5 was lower and that of Bm2, Bm29 and Bm3+Bm4 was higher in pSS patients compared to HD (all p&lt;0.05). When we divided patients according to the ESSDAI score (&lt;5 or ≥5) or to SG-GC (presence/absence), we observed for the first time that the percentage of Bm29 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 Bm29 persisted higher in pSS patients (p&lt;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&lt;5 (p=0.02). <h3>Conclusions</h3> We demonstrated for the first time that a subset of circulating mature B-cells, Bm29, 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. <h3>References</h3> 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 Sjögren9s syndrome. Expert Rev Clin Immunol. 2014;10:483–99. <h3>Disclosure of Interest</h3> None declared