Background/Purpose: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by immune cell infiltration in the salivary glands resulting in ocular and oral dryness. Abnormalities in both B and T follicular helper (Tfh) cells associated with ectopic germinal center formation in the salivary gland has been described in pSS. However, the diversity of Tfh cells and relationship between B and T cell subsets has not been fully elucidated. In this study, we examined the expression of ICOS and PD-1, two critical immune co-regulatory molecules for T follicular helper function, on memory T cells in both CXCR5⁺ (Tfh) and CXCR5^– (Tph) populations in pSS compared to HC, SLE and RA. We evaluated changes in peripheral blood B and T cell populations in pSS compared to other diseases and healthy controls.

Methods: pSS, SLE and RA patients, along with age and gender matched HC were recruited at University of Rochester. pSS (n=40), SLE (n=19) and RA (n=20) were classified based on ACR criteria. PBMCs were isolated by Ficoll-Hypaque and the frequencies of B and T subpopulations measured by multi-parameter flow cytometry. The mean+/- SEM was calculated for each cell population and statistical analysis was done by t-test. Correlation analysis was done by Pearson method, p < 0.05 was considered significant.

Results: pSS and SLE had significantly higher frequency of both CXCR5⁺PD-1⁺ICOS⁺ (PD-1⁺ICOS⁺ Tfh) and CXCR5^–PD-1^hiICOS⁺ (ICOS⁺ Tph) than HC, while RA and SLE had higher percent of CXCR5^–PD-1^hi (Tph) than HC. Further evaluation of Tfh subsets (based on CXCR3 and CCR6), revealed higher frequency of PD-1⁺ICOS⁺ Tfh1 and PD-1⁺ICOS⁺ Tfh2 in pSS and SLE compared to HC. In addition, we evaluated PD-1⁺ICOS^– Tfh populations that have been shown to have B cell helper functions. PD-1⁺ICOS^– Tfh1 and PD-1⁺ICOS^– Tfh2 were expanded in pSS and RA compared to HC, while RA patients also showed expansion of PD-1⁺ICOS^– Tfh17. Characterization of B cells in pSS patients revealed significant contractions of switched memory (SM), un-switched memory (USM) and double negative memory (DN) B cell compared to HC. In contrast, the fraction of activated memory B cells (CD95+ or CD21-) was significantly higher in pSS compared to HC. Additionally, the frequency of activated CD27+ memory B cell were positively correlated with frequency of PD-1⁺ICOS⁺ Tfh and ICOS+ Tph. The frequency of ICOSL+ B cells was positively associated with the frequency of PD-1⁺ICOS^– Tfh17 (r=0.362, p=0.024), a putative B cell helper Tfh subset. We are currently evaluating transcriptomic and proteomic data from these patients to correlate with flow cytometry data and to further elucidate the interaction between the B cell and T cell compartment in pSS.

Conclusion: Our data highlight the significant abnormalities in the peripheral Tfh and B cell compartment in pSS and the critical role of Tfh-B cell interactions. The association between ICOSL+ memory B cells and ICOS+ T cells suggests their potential interaction in germinal center-like structures in salivary glands.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expansion-of-activated-pd-1-icos-t-follicular-and-peripheral-helper-cells-in-primary-sjogrens-syndrome-associates-with-abnormalities-in-b-cell-compartment/