ABNORMITY TFH SUBSETS INDICATE DISEASE ACTIVITY WHILE SIROLIMUS THERAPY RESTORES THE PD-1+ICOS+TFH/ACTIVATED TFR BALANCE IN PRIMARY SJOGREN’S SYNDROME PATIENTS

Background: Immune imbalance between follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells is a characteristic of primary Sjogren’s syndrome (pSS) [1]. The heterogeneity among Tfh and Tfr can be elucidated by separating them into different subsets based on the expression molecular characteristics. Objectives: The aim of this study was to investigate the role of Tfh and Tfr subsets, and to evaluate the effects of sirolimus on these cells. Methods: In this study, we enrolled 51 pSS patient and 26 healthy controls (HCs), and analyzed the frequencies and absolute counts of circulating Tfh and Tfr subsets, and serum levels of cytokines. Within these patients, analyses of above T cells in twelve patients before and after treatment with sirolimus. Clinical indicators and correlations with follicular T cells were systematically analyzed. The diagnostic value for CD4+CXCR5+T cells was evaluated by the areas under the receiver operating characteristic curves (AUC). Results: Patients with pSS had higher frequencies and absolute numbers of PD-1+ICOS+Tfh cells, but lower levels of activated Tfr cells cells, thereby resulting in elevated ratios of PD-1+ICOS+Tfh/activated Tfr. In addition, PD-1+Tfh cells levels were lower in pSS patients than in HCs. Interestingly, the ratio of PD-1+ICOS+Tfh/activated Tfr was a strong predictor of pSS diagnosis. However, sirolimus therapy resulted in significant reductions in PD-1+ICOS+Tfh cells and the PD-1+ICOS+Tfh/activated Tfr ratio in pSS patients. We also found increased numbers of PD-1+ICOS+Tfh cells were associated with B cells, while decreased numbers of Tfr and their subsets were strongly associated with aTreg cells in pSS patients. The ESSDAI [2] was positively correlated with PD-1+ICOS+Tfh cell frequency, but was negatively correlated with PD-1+Tfh cell count. Conclusion: These findings suggest that the PD-1+ICOS+Tfh cell:activated Tfr cell ratio and PD-1+Tfh cells constitute potential novel biomarkers for pSS, and Tfr cells and subsets resemble derived aTreg cells. Furthermore, the PD-1+ICOS+Tfh cells as a biomarker of disease activity and provide new ground to verify the therapeutic implications of sirolimus as an innovative drug in pSS. REFERENCES: [1]Fonseca VR, Romão VC, Agua-Doce A, Santos M, López-Presa D, Ferreira AC, et al. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjogren’s Syndrome. Arthritis Rheumatol 2018; 70:774-784. [2]Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 2010; 69:1103–9. Disclosure of Interests: None declared Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 1035Session: SLE, Sjön’s and APS - treatment (Poster Presentations)