According to cohort study data results published in Rheumatology, elevated interleukin-18 (IL-18) levels were associated with increased disease activity and history of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA). IL-18 has been shown to have clinical validity as a biomarker for sJIA activity and MAS.
Investigators recruited 40 patients with sJIA from the Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. Total IL-18, CXCL9, and S100 protein levels were calculated from blood serum samples. Patients were considered to have active disease if they had any of the following features at the time of sample collection: active arthritis, systemic features including rash and fever, and elevated erythrocyte sedimentation rate or elevated C-reactive protein levels. Clinically inactive disease (CID) was defined based on the Wallace criteria. History of MAS was determined based on past diagnosis by the treating physician. Receiver operating characteristic analysis was used to quantify the performance of serum IL-18 in predicting disease activity or prior MAS diagnosis.
Among 40 patients with sJIA, 21 had CID at the time of determination of IL-18. Median IL-18 levels were significantly higher in patients with active sJIA (16,499 pg/mL; interquartile range [IQR], 4816-61,839) compared with those with CID (P =.0004). IL-18 levels were also elevated in the majority (79%) of patients with CID (median, 1164 pg/mL; IQR, 587-3444). Patients with a history of MAS had significantly higher median IL-18 levels (13,380 pg/mL; IQR, 4212-62,628) compared with those without MAS history (956.5 pg/mL; IQR, 276.3-4626.5). Total IL-18 measurements performed well in predicting disease activity and history of MAS, with area under the curve values of 0.8145 and 0.84, respectively. A moderate correlation was observed between IL-18 and other sJIA biomarkers, including CXCL9 (P =.0002), S100A8/A9 (calprotectin; P =.002), and S100A12 (calgranulin C) proteins (P =.003). Among patients for whom serum ferritin levels were available (n=22), a strong correlation was observed between IL-18 and ferritin (P <.0001). When stratified by disease activity, IL-18 and ferritin levels maintained a strong correlation among those with active disease only.
These data support the validity of serum IL-18 as a biomarker for both sJIA and MAS, particularly among patients with active disease. Elevated IL-18 levels may precede an increase in disease activity or development of MAS, although further research is necessary to explore the performance of IL-18 as a biomarker.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Yasin S, Fall N, Brown RA, et al. IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome [published online July 20, 2019]. Rheumatology. doi:10.1093/rheumatology/kez282