Frequency of CD4⁺CXCR5⁺CD127^(lo) TFR cells in patients with rheumatoid arthritis

Dysregulation of Tfh and Tfr cells has been identified in rheumatoid arthritis (RA), yet inconsistent findings remain across existing studies. Accordingly, we investigated peripheral blood lymphocytes, CD4⁺ T cells, Treg, Tfh and Tfr subsets in untreated RA patients, treated RA patients and healthy controls to clarify their dynamic alterations in RA progression.

A total of 27 newly diagnosed, untreated RA patients (N-RA), 10 matched treated RA patients (P-RA) and 14 healthy controls (HCs) were included. Peripheral blood proportions of lymphocytes, CD4⁺ T cells, Treg, Tfh and Tfr were determined by flow cytometry, while serum Fgl2 levels were measured via ELISA. Intergroup differences in these markers were subsequently analyzed.

Fgl2 levels were significantly higher in the RA group than in HCs (20.74% vs. 13.90%, P = 0.002), whereas no statistically significant differences were observed across the three groups (N-RA, P-RA and HCs).Tfr frequencies were notably higher in N-RA patients than in P-RA (4.56% vs 3.16%, P = 0.001) and HCs (4.56% vs 2.81%, P < 0.001), with no obvious difference between P-RA and HCs. Consistent results were detected in paired pre- and post-treatment RA samples (4.99% vs 3.01%, P = 0.015). Tfr proportions showed no obvious correlations with clinical parameters.

Fgl2 may not serve as an ideal biomarker for RA. The frequency of Tfr cells was notably elevated in N-RA patients and declined significantly following therapeutic intervention. Given the absence of significant correlations between Tfr levels and clinical indicators, we hypothesized that anti-rheumatic therapy could normalize elevated Tfr levels. Key Points • Tfr cells are significantly increased in newly diagnosed RA. • Anti-rheumatic therapy significantly corrects the imbalance of Tfr cells in RA.