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Objective. Receptor for advanced glycation end products (RAGE) serves as a pattern recognition receptor for several endogenous ligands that are potent inducers of inflammation. By activating endothelial cells and leukocytes, RAGE augments recruitment of leukocytes to sites of inflammation, which is a key process, especially in vasculitis. Soluble RAGE (sRAGE) acts as a naturally occurring inhibitor of RAGE by neutralizing proinflammatory ligands, e.g., S100A12. This neutrophil-derived protein has been reported to be associated with Kawasaki disease (KD) and to provoke proinflammatory responses. The aim of this study was to investigate circulating sRAGE in an acute inflammatory disorder and to compare these data directly with concentrations of the proinflammatory RAGE ligand S100A12.Methods. Serum concentrations of sRAGE and S100A12 were analyzed by specific enzyme-linked immunosorbent assays in 50 children with KD, and additionally in 39 patients with juvenile idiopathic arthritis (JIA). In 28 of the patients with KD, levels were analyzed longitudinally over the course of the disease.Results. Patients with KD and those with systemic-onset JIA had decreased levels of sRAGE during active disease, especially those patients with KD who were more severely affected and not responding to treatment. In addition, the level of sRAGE correlated negatively with the level of proinflammatory S100A12. After intravenous immunoglobulin (IVIG) therapy in patients with KD, the S100A12:sRAGE ratio was significantly different between responders and nonresponders.Conclusion. Inverse regulation of both sRAGE and its proinflammatory ligand S100A12 seems to be a relevant molecular mechanism promoting systemic inflammation. Calculating the S100A12:sRAGE ratio might help to detect patients with KD who are at risk of being unresponsive to IVIG therapy.Kawasaki disease (KD) is an acute vasculitis of infants and children predominantly affecting small-and medium-sized arteries, particularly the coronary artery. Boys younger than age 1 year are at special risk for fatal disease due to coronary artery lesions. Both the etiology and pathogenesis of KD remain unclear, but data from recent studies suggest that S100 proteins are involved in inflammation and endothelial cell damage in KD (1). Histopathologic studies have shown that the coronary lesions are characterized by microvascular dilatation, endothelial cell injury, and platelet aggregation with thrombosis in the small arterioles (2). In addition, transient infiltration by neutrophils is a key phenomenon in the early stage of acute KD, prior to infiltration of

We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KD, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14-positive circulating endothelial cell may predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.

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