Abstract
Background: Primary Sjo spacing diaeresis gren's syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands. The current study was performed to investigate the roles of follicular helper T (Tfh) and follicular regulatory T (Tfr) subsets in patients with pSS, and to evaluate the effects of sirolimus on these cells. Methods: Levels of circulating Tfh and Tfr subsets in 58 pSS patients and 26 healthy controls (HC) were deter-mined by flow cytometry. These T cell subsets were also analyzed in 12 patients before and after treatment with sirolimus. Clinical features and correlations with follicular T cells were analyzed systematically. The discrimi-native ability of the cells and ratios was evaluated based on the area under the receiver operating characteristic curves. Results: Patients with pSS had higher percentage and absolute number of PD-1+ICOS+Tfh cells, while lower percentage and absolute number of Tfr, activated regulatory T (aTreg) cells, and CD45RA-Foxp3(high) activated Tfr cells. Furthermore, increased number of PD-1+ICOS+Tfh cells was associated with B cells, while decreased numbers of Tfr and their subsets was strongly associated with aTreg cells in pSS patients. Also, the higher proportion of PD-1+ICOS+Tfh cells was positively correlated with higher level of autoantibodies, ESR, IgG, cytokines (IL-2, IL-4, IL-10, IL-17, IFN-gamma, TNF-alpha, IL-21 and sIL-2 alpha R), and disease activity. Unexpectedly, the elevated PD-1+ICOS+Tfh:CD45RA-Foxp3(high) activated Tfr ratio had the greatest ability to discriminate between pSS and HC, and sirolimus therapy restored the PD-1+ICOS+Tfh cells:CD45RA-Foxp3(high) activated Tfr ratio, and controlled disease activity. Conclusion: The novel ratio of PD-1+ICOS+Tfh to CD45RA-Foxp3(high) activated Tfr cells can effectively discriminate the pSS patients from controls, and Tfr cell subsets may resemble Treg cell lineages. Furthermore, the PD-1+ICOS+Tfh cells can be used as a biomarker of disease activity and to verify the therapeutic effects of sirolimus in pSS.
NSTL
Elsevier