Pathogenesis and therapeutic strategy of Kawasaki disease : Gene expression determined by microarray study

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Background: Although high-dose intravenous immunoglobulin (IVIG) treatment in the acute stage of Kawasaki disease (KD) has shown to be effective, 10% to 20% of severe KD patients are resistant to initial IVIG treatment. We could predict these severe KD patients using Kurume score for evaluation score of severity of KD (J. Pediater, 2006). We analyzed RNA expression of whole blood s of KD patients using microarray. We investigated relationship to gene expression and severity of KD and to assess the effect of therapeutic strategy by changes of gene expression before and after initial treatment Method: The gene expression of 11 KD patients at Kitasato University, from April 2007 to December 2007 were studied using microarray system. Those patients divided into 2 groups using Kurume scare (Cut off points; 3). 6 KD patients were severe cases (〓3), 5 KD patients were mild cases(〓2). In severe KD patients groups, we randomly divided into 2 groups by different initial treatment strategy 3 pati … More ents were treated with WIG therapy for initial treatment, another 3 patients were treated with MG therapy plus steroid pulse therapy(Methyl-prednisolone: 30mg/kg/day, 1day) for initial treatment. Result: Those were significant differences in gene expression between mild KD patients and severe KD patients. The 1226 genes of 66577 genes of severe cases were expression higher than those of mild cases. The Toll-like receptor signaling pathway associated genes, cytokine-cytokine receptor interaction associated genes were especially high expression in severe cases. The significant differences were found in the decreased gene expression between 3 patients with IVIG therapy for initial treatment and 3 patients with IVIG plus steroid pulse therapy for initial treatment. The 254 genes expression were decreased by WIG treatment, and 5249 gene expression were decreased by MG plus steroid pulse therapy. The WIG plus steroid pulse therapy widely suppressed gene expression related to inflammation. Conclusion: The present results demonstrated the merit of further investigation of the alteration as a source of base line information for the design of future strategy of KD vasculitis. Less