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 B cell activation and skewing of T cell polarization toward Th2 and T follicular helper (TFH) associated with ectopic germinal center formation in the salivary gland are observed in pSS. However, the interplay between B and T cell subsets, and other immune abnormalities, as well as relationship to disease status, has yet to be fully elucidated. In this study, we evaluated changes in peripheral blood B and T cell populations in pSS compared to SLE and RA diseases and healthy controls.

Methods: Two cohorts of patients with pSS according to European-American Consensus and ACR criteria and age-matched healthy controls (HC) were recruited (Rochester, USA and Strasbourg, France) and disease activity assessed by ESSDAI and ESSPRI. The Rochester cohort also included RA (n=20) and SLE (n=15) 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. Data are reported as median [25^th-75^th quartile]. Correlation analysis was done by Pearson method, p < 0.05 was considered significant.

Results: We examined the expression of ICOS and PD-1, two important co-regulatory molecules of the B7-family, on memory T cells (CD4+CD45RA-) in pSS compare to HC, SLE and RA. pSS and SLE had higher frequency of memory T cells expressing both ICOS and PD-1 than HC while RA had higher frequency of PD-1^+/hi T cells. Accordingly, T follicular helper cells (TFH: CXCR5⁺ICOS⁺PD-1⁺⁾ were found at higher frequency in pSS and SLE compared to HC (pSS (n=40): 5.96 [3.75-8.71]%; HC (n=58): 4.18 [2.51-4.91]%, p=0.0005; SLE (n=15): 4.61 [3.51-9.84]%, p=0.002). Further evaluation of TFH subsets (based on CXCR3 and CCR6), revealed higher frequency of TFH1 and lower TFH17 subset in pSS compare to HC and RA, also confirmed in the Strasbourg cohort. Characterization of B cells in pSS patients from Rochester cohort revealed significant contractions of switched memory (SM) and un-switched memory (USM) B cell compared to HC (pSS SM (n=39): 3.52 [1.65-7.28]%; HC SM (n=38): 7.57 [5.49-10.86]%, p=0.005; pSS USM (n=39): 10.07 [5.47-15.62]%; HC USM (n=38): 21.44 [15.16-31.27]%, p<0.0001). Furthermore, frequencies of ICOSL expressing SM and USM were lower in pSS than HC. There was a significant inverse correlation between ICOSL+ USM B cells and TFH1 in pSS patients (ρ= -0.55, p=0.0255). There were two distinct clusters of pSS based on T and B cell subsets, with one group distinct from HC and associated with higher disease activity and autoantibodies. In a subset of pSS (n=10), T and B cell frequencies were evaluated longitudinally at 6 months. Significant changes in frequency of ICOSL+ B cells were observed and negatively correlated with changes in CXCR5+ICOS+ T cells (ρ= -0.634, p=0.049).

Conclusion: Our data highlight the significant abnormalities in the peripheral TFH and B cell compartment in pSS and further suggest the critical role of TFH- B cell interactions. The decrease in ICOSL+ memory B cells suggests interaction with ICOS+ T cells in germinal center-like structures in salivary glands.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comprehensive-immuno-phenotyping-of-follicular-helper-t-cell-and-b-cell-subpopulations-in-primary-sjogrens-syndrome/