Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis

•Two subsets of s-JIA can be identified on the basis of serum IL-6/IL-18 levels.•IL-6-dominant subset was more likely to have more severe joint disease.•IL-18-dominant subset was more likely to develop MAS.•Serum IL-18 levels might be useful to predict MAS development.•The cutoff value of serum IL-18 levels to predict MAS development is 47750 pg/ml.

To assess the role of IL-6/IL-18 in the pathogenesis of systemic juvenile idiopathic arthritis (s-JIA) and to investigate the clinical significance of serum IL-18 levels for predicting macrophage activation syndrome (MAS) development, we measured the serum IL-6/IL-18 levels in 76 s-JIA patients, including 15 with MAS, and compared them with the clinical features. We identified 2 distinct subsets on the basis of serum IL-6/IL-18 levels. The IL-18-dominant subset had more patients who developed MAS. Serum IL-18 levels during active phase in patients with MAS were significantly higher than those without MAS. The cutoff value of serum IL-18 levels for predicting MAS development was 47750 pg/ml. The patients with IL-18 dominant subset at their disease onset were significantly more likely to develop MAS after TCZ therapy started. IL-18 might have a key role in the pathogenesis of MAS. Serum IL-18 levels > 47750 pg/ml might be useful to predict MAS development.