AB0148 Differential Peripheral B-Cell Phenotype in Patients with Primary Sjögren's Syndrome (PSS) Compared To Secondary Sjögren's Syndrome Associated with Systemic Lupus Erythematosus (SLE/SS)
Authors: N.L. Thompson, D.A. Isenberg, E. Jury, C. Ciurtin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Peripheral B-cell abnormalities are a feature of both lupus (SLE) and primary Sjogren9s syndrome (pSS). However, whereas patients with pSS have increased frequencies of Bm1/Bm2 (naïve), Bm29 (germinal centre founders) and Bm3–4 (centroblasts/centrocytes), but decreased Bm5 (memory) compared with healthy controls (HC), patients with SLE have increased Bm5 levels, which correlated with disease activity. No previous studies investigating the peripheral B-cell phenotype in patients with SLE and secondary SS (SLE/SS) are available. <h3>Objectives</h3> We questioned whether the defective B-cell phenotype in pSS patients was also present in patients with SS/SLE, and whether differences in B-cell phenotype could be related to changes in B-cell lipid-raft expression and BAFF-receptor function in pSS and SLE/SS patients. <h3>Methods</h3> Blood samples and clinical and laboratory parameters from 32 patients with pSS and SS/SLE and 13 age/sex matched HC were obtained. We used flow-cytometry to perform B-cell immunophenotyping and analysis of lipid-raft expression (marker of B-cell activation). <i>In vitro</i> cultures assessed lipid-raft expression in response to BAFF. <h3>Results</h3> Patients with SLE/SS had a district B-cell phenotype, characterised by decreased Bm1 and Bm5 and increased Bm2 populations compared to HC (p=0.031, p=0.035 and p=0.01, respectively), and increased Bm2 compared to pSS (p=0.027). Bm1-cells were decreased in both pSS and SLE/SS patients compared to HC (p=0.028 and p=0.031, respectively). Both age and disease duration correlated strongly with Bm29 cells in SLE/SS patients (r=0.9572, p=0.0428), and the immunosuppressive treatment correlated negatively with the number of circulating Bm2 and Bm29 cell in pSS (r = -0.54, p=0.01 and r = -0.56, p=0.008, respectively). B-cells from patients with pSS had a significant increase in lipid-raft expression compared to HC (p=0.01) and patients with SS/SLE (p&lt;0.05). Furthermore, lipid-raft levels correlated with BAFF-receptor expression in HC and SLE/SS B-cells (p=0.17, r=0.694) but not in pSS patients. Both disease activity score (ESSDAI) and IgG level correlated positively with lipid rafts expression in B cells from patients with pSS (r =0.79, p=0.004 and r =0.53, p=0.04, respectively). <h3>Conclusions</h3> We showed that patients with SLE/SS had more significant B-cell abnormalities compared to HC and pSS, detectable even in a small number of patients. Also the relationship between lipid-raft and BAFF-receptor expression was altered between pSS and SLE/SS patients, and correlated with the disease activity and Ig G levels in pSS group. Further studies will validate our findings and investigate whether B-cell lipid-rafts mediate differential BAFF-receptor signalling. <h3>References</h3> Bohnhorst JO, Bjorgan MB, Thoen JE, Natvig JB, Thompson KM. Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjogren9s syndrome. J Immunol. 2001; 167 (7):3610–8. Epub 2001/09/21. Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, et al. Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis and rheumatism. 2008; 58 (6):1762–73. Epub 2008/06/03. <h3>Disclosure of Interest</h3> None declared