Interleukin-15 as a Biomarker Candidate of Rheumatoid Arthritis Development

There is a need for definite diagnosis of rheumatoid arthritis (RA) at its earliest stages of development in order to introduce early and effective treatment. Here we assessed whether serum interleukin-15 (IL-15) can serve as a new biomarker of RA development in patients with undifferentiated arthritis (UA). Interleukin-15, IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) were measured in UA patients at inclusion. Six months later, the diagnosis was re-evaluated, and statistical analysis was performed. We found that at the UA stage, IL-15 was more prevalent in patients who progressed to RA than RF or anti-CCP Abs (83.3% vs. 61.1% and 66.7%, respectively). Interleukin-15 showed higher sensitivity (77.8%) than both autoantibodies and higher specificity (80.9%) than anti-CCP Abs in identification of UA patients who developed RA. The diagnostic utility of IL-15 was comparable to that of RF (AUC: 0.814 vs. 0.750, p > 0.05), but higher than that of anti-CCP Abs (AUC: 0.814 vs. 0.684, p = 0.04). The combined use of IL-15, RF and anti-CCP Abs yielded higher diagnostic accuracy for RA than autoantibodies determination only. Our results indicate that IL-15 can be used as a biomarker of RA development in patients with UA.