Decreased regulatory T-cell frequency and interleukin-35 levels in patients with rheumatoid arthritis

Interleukin-35 (IL-35) is a newly discovered anti-inflammatory cytokine predominantly released by regulatory T cells (Tregs) and may serve an important role in the pathogenesis of autoimmune diseases. The levels of IL-35 and corresponding Treg frequencies in patients with rheumatoid arthritis (RA) have scarcely been reported. The present study aimed to detect serum IL-35 levels and Treg frequencies in patients with RA, and analyze their association with each other and with indicators of RA. A total of 55 patients with RA, including 37 active-phase (AP) and 18 chronic-phase (CP) cases, as well as 20 healthy controls (HC), were recruited. Clinical parameters, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody and 28-joint disease activity score (DAS28) were assessed. The Treg frequency in peripheral blood (PB) was determined by flow cytometry. IL-35 mRNA in PB mononuclear cells of the patients with RA was measured by reverse transcription-quantitative polymerase chain reaction analysis, and IL-35 levels in the serum were detected by ELISA. The correlations between IL-35 levels and the abovementioned indexes were analyzed by determining Pearson's correlation coefficient. The results of the present study indicated that the Treg frequency was significantly decreased in patients with RA compared with that in HC. No significant difference in Treg frequency between the AP and CP groups of RA patients was identified. In addition, the serum IL-35 levels and mRNA expression in RA patients were obviously lower than those in the HC. Of note, the serum IL-35 levels were negatively correlated with the ESR and DAS28 of patients with RA, while no correlation with CRP, RF or anti-CCP antibodies was identified. In addition, a significant positive correlation was revealed between serum IL-35 levels and the Treg frequency. These results suggest that IL-35 and Tregs have a protective role regarding the development of RA.