The Role of Different Circulating T Follicular Helper Cell Markers in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic incurable inflammatory autoimmune disease. T follicular helper (Tfh) cells expressing different markers play critical roles in the development of RA. However, their specific mechanisms of action and association with RA clinical parameters are not clear. We therefore performed a cohort study to investigate the effects of different Tfh cell markers on RA pathogenesis. We retrospectively reviewed clinical data from 30 patients diagnosed with RA and 30 healthy controls (HCs) who visited our hospital. Based on X-ray findings, the patients were divided into a joint bone erosion group (n = 17) and a non-erosive joint bone group (n = 13). Using flow cytometry, we determined the frequencies of five peripheral blood CD4⁺ Tfh cell types characterized by different markers, and examined these cell types for correlations with clinical parameters. RA patients exhibited higher frequencies of CD4⁺CXCR5⁺, CD4⁺CXCR5⁺ICOS⁺, CD4⁺CXCR5⁺OX40⁺, and CD4⁺CXCR5⁺CD40L⁺ Tfh cells than HCs. CD4⁺CXCR5⁺, CD4⁺CXCR5⁺CD40L⁺, and CD4⁺CXCR5⁺OX40⁺ Tfh cell frequencies positively correlated with disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR), while those of CD4⁺CXCR5⁺ and CD4⁺CXCR5⁺CD40L⁺ Tfh cells were related to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies. In RA patients without joint bone erosion, CD4⁺CXCR5⁺CD40L⁺ Tfh cell frequencies were positively correlated with both RF and DAS28-ESR. Serum anti-CCP antibody levels and CD4⁺CXCR5⁺ICOS⁺ Tfh cell frequencies were also positively correlated. Circulating CD4⁺CXCR5⁺CD40L⁺ Tfh cells appear to play critical roles in RA pathogenesis, and restricting CD4⁺CXCR5⁺CD40L⁺ Tfh cells may be a therapeutic strategy for controlling RA.