The Correlation between Aire and ICOSL Expression in Peripheral Blood CD14+ Cells and Tfh Cells and Disease Activity in RA Patients

Background: Recent trans-ethnic genome-wide association study (GWAS) showed that autoimmune regulator (Aire) played a pivotal role in Rheumatoid Arthritis (RA). Our preliminary research showed that Aire can affect T follicular helper (Tfh) cells differentiation by regulating the expression of inducible costimulator molecule ligand (ICOSL) on DCs. The abnormal levels of Tfh cells are related to the pathogenesis of RA, which can promote autoantibody production by helping autoreactive B cells activation.Therefore, the abnormal expression of the Aire in RA patients may lead to increased expression of ICOSL, promoting the differentiation of Tfh cells and the secretion of autoantibodies, consequently resulting in RA. However, to date, changes in the Aire, Tfh cell, and ICOSL levels in the peripheral blood of RA patients have not been reported. This study assessed the expression level of Aire and ICOSL and the number of Tfh cells in the peripheral blood of patients with RA and then explored the relationship between these three factors and RA severity. We are attempting to further explore the pathogenesis of RA to develop targeted treatments. Methods: : Fifteen RA patients were enrolled, basic clinical information of the patients was collected, blood samples were collected to examine the Aire expression, ICOSL expression and CD4 + CXCR5 + PD1 + (Tfh cell) numbers in circulation before treatment. The relationship between these three factors and RA severity was explored. Results: : This study showed that compared with the control group, the levels of circulating Aire in RA group significantly reduced, while the ICOSL expression levels and Tfh cell numbers in the peripheral blood of RA group were increased. Additionally, the Aire expression levels were negatively correlated with the ICOSL expression levels and Tfh cell numbers, and the ICOSL expression levels were positively correlated with Tfh cell numbers. Moreover, the Aire and ICOSL expression levels and Tfh cell numbers were correlated with anti-cyclic citrullinated peptide antibodies (ACPA) levels and disease activity score in 28 joints (DAS28). Conclusions: : These results suggested the abnormal Aire gene expression in RA patients may affect Tfh differentiation by regulating the expression of ICOSL, leading to the autoantibodies production and promote the onset of RA.