POS0818 IN PRIMARY SJÖGREN’S SYNDROME CCR9/CXCR5 CO-EXPRESSING EFFECTOR CD4 T CELLS ARE INCREASED AND ARE ENRICHED IN PD-1/ICOS-EXPRESSING T CELLS

Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by B cell hyperactivity. CXCR5+ follicular helper T cells (Tfh), CXCR5-PD-1hi peripheral (Tph) and CCR9+ Tfh-like have been implicated in driving hyperactivity pSS (1-3), however, their potential overlap has not evaluated. Objectives To study the between two CXCR5- subsets to PD-1/ICOS expression, hall mark markers, as compared “true” CXCR5/PD-1/ICOS-expressing Tfh cells. Methods We defined Tph memory (CD45RO+), CXCR5-CCR9+, CXCR5+CCR9+ CD4 cells, previously described. co-expressing were specified on phenotype. memory, CXCR5+PD-1+ICOS+ populations from blood mononuclear of patients (n=12) age- gender-matched healthy controls (HC, n=11) flow cytometry. expression these was each other taking into account differentiation status. Results In number significantly increased HC (median 0.53% versus 0.23% p=0.049). Also elevated HC, i.e. approximately 2.7% 1.7% (medians, p=0.019). CCR9 equally distributed Only a modest 2.1% (1.2-3.2%) expressed with interquartile range), indicating limited overlap. (Tfh) highest frequency PD-1hi either or without co-expression (PD-1hi differed CXCR5-CCR9- CXCR5-CCR9+ both p<0.0001.) No difference seen CXCR5+CCR9- (p=0.57). Within populations, expressing CXCR5 and/or showed trend higher ICOS HCs, but this only significant (28.6% 55%, medians for respectively, p=0.02) CCR9. However, found CXCR5/CCR9 which are enriched circulation patients. PD-1, ICOS, than CCR9- (in all three comparisons p<0.05). Conclusion distinct that can drive pSS. The known upregulated CCL25 CXCL13, ligands CXCR5, at inflammatory sites suggests concerted action facilitate migration frequencies positive Hence, effector may contribute ongoing immune responses References [1]Chen W, Yang F, Xu G, Ma J, Lin J. Follicular regulatory immunopathology primary syndrome. Journal Leukocyte Biology. 2021 Feb 1;109(2):437–47. [2]Blokland SLM, Hillen MR, Kruize AA, Meller S, Homey B, Smithson GM, et al. Increased Helper Cells Expressing Salivary Glands Patients With Syndrome: Potential New Axis Lymphoid Neogenesis. Arthritis & Rheumatology. 2017 Oct;69(10):2038–51. [3]Pontarini E, Murray-Brown WJ, Croia C, Lucchesi D, Conway Rivellese Unique expansion IL-21+ under control identifies ectopic germinal centres MALT lymphoma. Ann Rheum Dis. 2020;79:1588–99. Acknowledgements: NIL. Disclosure Interests None Declared.