Low Serum Levels of Interleukin 35 in Patients with Rheumatoid Arthritis

Interleukin 35 (IL-35) is a newly discovered anti-inflammatory cytokine. Recent studies have indicated that it plays a crucial role in the pathogenesis of autoimmune diseases. In humans, IL-35 is predominantly secreted from regulatory T cells. This study aimed to measure serum IL-35 levels in patients with rheumatoid arthritis (RA) and in control individuals, and analyze its association with disease indicators of RA. One hundred patients with RA were recruited, and 50 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured using an enzyme-linked immunosorbent assay kit. RA patients showed significantly lower serum levels of IL-35 compared with healthy controls (p < 0.001). RA patients suffering from erosive arthritis (n = 31) had lower IL-35 levels than those with non-erosive arthritis (n = 69, p = 0.022). In addition, serum IL-35 level was significantly lower in 22 patients with elevated percentage (> 75%) of neutrophils (p < 0.001). Correlation analysis indicated a significantly negative association between IL-35 and age, rheumatoid factor (RF), or percentage of neutrophils. In contrast, the serum IL-35 levels were not significantly different between patients with anti-cyclic citrullinated peptide (CCP) antibodies (n = 78) and those without anti-CCP antibodies (n = 22). However, among patients without anti-CCP antibodies, the serum IL-35 levels were lower in patients with erosive arthritis (n = 8) than those patients without erosion (n = 14) (p < 0.001), although no significant difference was detected in patients with anti-CCP antibodies. In conclusion, IL-35 plays a protective role in the pathogenesis of RA.