AB0020 Expression levels of signaling lymphocyte activation molecule family 6 (SLAMF6) on circulating follicular helper T cells are associated with disease activity in systemic lupus erythematosus
Authors: SE Kang, SJ Lee, DJ Go, HM Kwon, EY Ahn, JK Park, EY Lee, EB Lee, YW Song
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> T follicular helper cells (Tfh) are necessary for B-cell maturation and differentiation in the germinal centers (GC). The signaling lymphocyte activation molecule family (SLAMF) receptors on the cell surface mediate T cell:B cell interaction for formation and maintenance of GC. But it remains to be elucidated whether SLAMF is expressed in circulating T follicular helper cells (cTfh). <h3>Objectives</h3> The aim of this study was to investigate the levels of SLAMF3 and SLAMF6 on cTfh and to analyze their association with disease activity in systemic lupus erythematosus (SLE) patients. <h3>Methods</h3> Blood samples were collected from 50 SLE patients, 24 Sjogren9s syndrome (SS) patients and 25 age- and sex-matched healthy controls (HCs). In this study, CXCR5, programmed cell death protein 1 (PD-1), and CD4 were used as markers to define cTfh in peripheral blood mononuclear cells (PBMCs). The expression levels of SLMAF3 and SLMAF6 on cTfh were compared to that of circulating B cell subsets by flow cytometry. Clinical features including disease activity and laboratory tests were analyzed according to expression of SLAMF3 and SLAMF6. <h3>Results</h3> Surface expression of SLAMF6 on CD4 T cells was significantly increased in SLE patients compared to SS patients (mean fluorescence intensity [MFI], mean ± SD: 1291±319 vs 1098±147, p=0.015) and HCs (1291±319 vs 1094±243, p=0.011). But there was no difference in expression of SLAMF3 on CD4 T cells between SLE patients and SS patients or HCs. SLAMF6 expressions on cTfh cells, identified as CD4<sup>+</sup>CXCR5<sup>+</sup>PD-1<sup>+</sup>, were significantly increased in SLE patients than in SS patients (1500±270 vs 1296±140, p=0.001) and HCs (1500±270 vs 1295±161, p=0.001). SLAMF6 expressions on cTfh cells had correlation with systemic lupus erythematosus disease activity index (SLEDAI) (Spearman9s rho=0.477, p=0.001), proteinuria (rho=0.321, p=0.030) and double strand DNA (rho=0.340, p=0.026) in SLE patients. Moreover, expression levels of SLAMF6 on cTfh cells were correlated with those of several B cell subsets including total B cells (CD19<sup>+</sup>), naïve B cells (CD19<sup>+</sup>CD27<sup>-</sup>IgD<sup>+</sup>) and class-switched memory B cells (CD19<sup>+</sup>CD27<sup>+</sup>IgD<sup>-</sup>). But SLAMF6 expressions of B cell subsets were not correlated with disease activity. <h3>Conclusions</h3> Surface expression of SLAMF6 was increased in cTfh cells in patients of SLE and had correlation with disease activity. <h3>References</h3> T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity. 2013;17;39(4):770–81. Choi JY, His-enHo J, Pasoto SG, et al. Circulating follicular helper-like T cells in systemic lupus erythematosus: association with disease activity. Arthritis Rheumatol. 2015;67(4):988–99. Zhang X, Lindwall E, Gauthier C, et al. Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production. Lupus. 2015;24(9):909–17. <h3>Disclosure of Interest</h3> None declared