Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children

Objectives. To compare the cytokines involved in the development of macrophage activation syndrome (MAS) in different background rheumatic diseases and to identify serum biomarkers for MAS diagnosis. Methods. Serum neopterin, IL-6, IL-18 and soluble TNF receptor (sTNFR) type I (sTNFR-I) and type II (sTNFR-II) levels were determined using ELISA in 12 patients with SLE, including five with MAS; 12 patients with JDM, including four with MAS; 75 patients with Kawasaki disease (KD), including six with MAS; and 179 patients with systemic JIA (s-JIA), including 43 with MAS. These results were compared with the clinical features of MAS. Results. Serum neopterin, IL-18 and sTNFR-II levels were significantly higher during the MAS phase than during the active phase in patients with all diseases. Furthermore, serum sTNFR-I levels were significantly higher during the MAS phase than during the active phase in patients with SLE, KD and s-JIA. Receiver operating characteristic (ROC) curve analysis revealed that serum sTNFR-I levels for SLE, serum IL-18 levels for JDM, and serum sTNFR-II levels for KD and s-JIA had the highest areas under the ROC curve. Serum levels of these cytokines were significantly and positively correlated with serum ferritin levels. Conclusions. Overproduction of IFN-gamma, IL-18 and TNF-alpha might be closely related to the development of MAS. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA might be useful diagnostic markers for the transition from active phase to MAS.

Automated summary

This study compared the cytokines involved in the development of macrophage activation syndrome (MAS) in different rheumatic diseases and identified that serum neopterin, IL-18, and sTNFR-II levels were significantly higher during the MAS phase. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA may serve as useful diagnostic markers for the transition from active phase to MAS.