Objective: To detect the expressions of T follicular helper (Tfh) subsets and T follicular helper effect memory (Tfhem) cells in circulation of patients with rheumatoid arthritis (RA), as well as to examine their roles in providing biomarkers for active RA.
Methods: This study enrolled 41 patients with RA, who were navely-treated or had no application of hormone and disease-modifying anti-rheumatic drugs in recent 3 months, as well as 32 healthy controls. The percentages of Tfhem (CD4+CXCR5+CCR7lowPD1high) cells, Tfh (CD3+CD4+CXCR5+CD45RA-) subsets, Tfh1 (CXCR3+CCR6-Tfh),Tfh2 (CXCR3-CCR6-Tfh),and Tfh17 (CXCR3-CCR6+Tfh), were determined by flow cytometry of peripheral blood from the patients with RA and health controls. Serum levels of cytokines were detected by enzyme-linked immunosorbent (ELISA). The correlations of Tfhem/Tfh subsets with clinical indicators were analyzed.
Results: The mean age of the patients was (56.1±14.0) years (range: 20-82 years), the mean disease duration was (8.2±8.1) years. There was no significant difference between the RA patients and the health controls with age and gender. As compared with the health control, the percentage of Tfhem was significantly increased in the peripheral blood of the RA patients (12.8%±5.7% vs. 8.7%±2.0%, P=0.001). Moreover, the increased Tfhem was correlated with the higher disease activity score in 28 joints (DAS28) and erythrocyte sedimentation rate (ESR), but not with other clinical indicators, such as C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factors (RF). In addition, the percentage of Tfh2 subset, but not Tfh1 or Tfh17, was significantly increased in the RA patients (3.002%±0.408% vs. 1.730%±0.160%, P=0.013). As compared with Tfh2-low group, serum levels of Ig (immunoglobulin) A [(3.045±0.261) g/L vs.(3.963±0.815) g/L, P=0.172], IgG [(13.800±0.862) g/L vs.(16.980±0.224) g/L, P=0.161], IgM [(1.135±0.083) g/L vs.(1.731±0.380) g/L, P=0.140], IL (interleukin)-4 [(2.322±0.214) ng/L vs.(3.994±0.751) ng/L, P=0.056] and IL-10[(1.898±0.105) ng/L vs. (3.125±0.880) ng/L, P=0.140] in Tfh2-high group tended to increase with no significant statistical difference.
Conclusion: Our data suggest that Tfhem is associated with disease activity and is a valuable marker for active RA. It also presents a potential pathogenesis in the development of RA and the target for future therapies. Meanwhile, the increased Tfh2 and associated cytokines might be involved in the development of RA.