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 cell subsets, T cells, 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 patients compared to disease 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). The Rochester cohort also included rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (n=9 and 10 respectively) 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 as further defined in the results. Data are reported as median [25^th-75^th quartile].

Results: pSS patients from the Rochester cohort had a higher frequency of circulating TFH (CXCR5+ICOS+PD1+) than HC (pSS (n=15): 5.83 [4.38-8.13]%; HC (n=27): 4.18 [2.95-4.58]%, p=0.002). Although there was no significant difference in the relative frequency of TFH subpopulations (TFH1, TFH2, TFH17 and TFH1-17) between pSS, HC, RA, and SLE, the frequency of TFH1 ICOS+ PD1+ cells was significantly higher in pSS than HC (pSS (n=15): 7.29 [5.51-10.8]%; HC (n=27): 4.44 [3.2-5.86]%, p=0.001). pSS patients from the Strasbourg cohort had an increase in the frequency of circulating TFH (CD4+CD45RA- CXCR5+) in comparison to HC (pSS (n=48): 27.65 [20.45-34.1]%; HC (n=217): 21.70[18.02-26.11]%, p=0.02). The frequency of TFH1 cells was significantly higher in pSS than HC (pSS (n=48) 29.1 [25.5-33.9]; HC (n= 24): 24.01 |19.7; 31.5]%, p= 0.04). In the Rochester cohort, we characterized B cell populations. pSS patients had a significant reduction in switched memory (SM) B cells (CD27+IgD-) compared to HC (pSS (n=16): 3.94 [2.68-7.18]; HC (n=28): 8.95 [6.2-14.22]% of B cell, p=0.001). In similar fashion, the frequency of unswitched memory B cell (CD27+IgD+) in pSS was significantly lower than HC (pSS (n=16): 8.69 [4.71-13.99]; HC (n=28): 16.91 [12.98-21.36]% of B cell, p=0.003). We also observed significant reductions in frequencies of CD95+ SM B cells (pSS (n=16): 1.87 [0.93-2.88]; HC (n=28): 3.29[2.13-5.11]% of B cell, p=0.0037) and ICOSL+ SM B cells (pSS (n=16): 0.075 [0.05-0.28]; HC (n=28): 0.28 [0.17-0.84]% of B cell, p=0.01).

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+ SM B cells suggests their interaction with ICOS+ T cells in germinal center-like structures in salivary glands. Relationship to clinical parameters and pathologic and ultrasound abnormalities in salivary glands are currently under investigation.

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