OP0328 COMPARISON OF SERUM CYTOKINE PROFILE IN MACROPHAGE ACTIVATION SYNDROME AMONG DIFFERENT BACKGROUND RHEUMATIC DISEASES IN CHILDREN:

Abstract

Background Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of pediatric rheumatic diseases. MAS occurs most often in children with systemic juvenile idiopathic arthritis (s-JIA) and less commonly in children with systemic lupus erythematosus (SLE), Kawasaki disease (KD) and juvenile dermatomyositis (JDM). The hallmark of MAS includes uncontrolled and dysfunctional immune responses involving continual activation and expansion of T lymphocytes and macrophages, which in turn lead to marked hypercytokinemia. However, it is still unknown which cytokines play a key role in the pathogenesis of MAS among different backgrounds. Objectives This study was aimed to clarify cytokines involved in the development of MAS among different background rheumatic diseases and to identify the serum biomarkers for the diagnosis of MAS. Methods Serum neopterin, interleukin (IL)-18, IL-6, tumor necrosis factor (TNF)-α and soluble TNF receptor type I (sTNFR-I) and sTNFR-II levels were determined using enzyme-linked immunosorbent assay in 112 s-JIA patients including 30 with MAS, 8 SLE patients including 3 with MAS, 67 KD patients including 4 with MAS, and 7 JDM patients including 3 with MAS. Cytokine profiles in MAS phase of each disease were compared to those in active phase. Results Serum neopterin levels in patients with s-JIA, SLE and KD were significantly elevated in MAS phase compared to those in active phase. Serum neopterin levels in patients with JDM were also elevated in MAS phase compared to those in active phase, although statistically significant. Serum sTNFR-I levels in patients with s-JIA and SLE were significantly elevated in MAS phase compared to those in active phase. Serum sTNFR-I levels in patients with KD and JDM were also elevated in MAS phase compared to those in active phase, although statistically significant. Serum sTNFR-II levels in patients with s-JIA and KD were significantly elevated in MAS phase compared to those in active phase. Serum sTNFR-II levels in patients with JDM were also elevated in MAS phase compared to those in active phase, although statistically significant. Serum IL-18 levels in patients with s-JIA were significantly elevated in both active and MAS phase compared to those in patients with other diseases. There were no significant differences of serum IL-6 and TNF-α levels among different backgrounds. Conclusion The elevation of serum neopterin levels was the common finding in patients with MAS even in different backgrounds. These findings indicate that overproduction of interferon (IFN)-γ might be closely related to the development of MAS. Serum neopterin levels which reflect IFN-γ production might be a promising biomarker for the disease activity of MAS.