Plasma interleukin-38 in patients with rheumatoid arthritis

Previous studies have indicated that interleukin-38 (IL-38) is involved in rheumatoid arthritis (RA). The present study aims to assess plasma levels of IL-38 in RA and discuss the potential of IL-38 as a biomarker for RA. Protein concentrations of IL-38 were examined by enzyme-linked immunosorbent assay, and the mRNA level of IL-38 was tested by quantitative real-time polymerase chain reaction. Plasma IL-38 was first compared in a training cohort, including 130 RA patients and 53 healthy controls, given the optimal cutoff. Then, we validated the levels of IL-38 in a further cohort of 519 patients, including 250 with RA, 63 systemic lupus erythematosus, 62 primary Sjogren's syndrome, 51 gout, 63 osteoarthritis, and 30 psoriatic arthritis, as well as 60 healthy controls. To further discuss the changes in IL-38 after treatment and the relationship with disease activity, we tested IL-38 expression in RA patients from the training cohort under follow-up. In the training cohort, plasma levels of IL-38 were higher in RA patients compared with healthy controls (681.00 [234.45-826.47] versus 152.04 [70.06-246.80] pg/mL, P < 0.001). The IL-38 mRNA level was elevated in RA patients as compared with healthy controls (P < 0.001). Expression of IL-38 was significantly higher in RA patients compared with that in non-RA patients in the validation cohort (all P < 0.001). Treatment significantly reduced IL-38 expression. IL-38 expression was related to parameters of inflammation both at baseline and in the follow-up studies. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be a potential biomarker for RA. At the optimal cutoff value of 341.90 pg/mL, the sensitivity, specificity, and AUC were 72.30%, 90.60%, and 0.840, respectively, in the training cohort. Similar results were noted in the validation cohort. In conclusion, IL-38 expression correlated with RA disease activity, and plasma IL-38 might be a promising diagnostic biomarker for RA.