Abstract 14385: The Pathophysiology of Infliximab Treatment for Kawasaki Disease Patients A Microarray Study of Gene Expression
Background: Approximately 20% of Kawasaki disease (KD) patients are resistant to initial intravenous immunoglobulin (IVIG). Infliximab (IFX) is used to treat refractory KD. However, the pathophysiology of IFX for refractory KD is still unclear. This study investigated the mechanism of IFX treatment for refractory KD by examining the gene expression, serum cytokines levels, and vascular endothelial growth factor (VEGF) levels.
Methods: All patients were enrolled in the Department of Pediatrics, at Kitasato University. The patients were divided into 2 groups, comprising 9 refractory KD patients treated with IFX (group A) and 9 patients treated with initial IVIG (group B). Group A patients were given IFX (5 mg/kg) after two courses of IVIG (total 4 g/kg), All group B patients responded to the initial IVIG (2 g/kg).Whole blood was collected from the KD patients in the 2groups before and 36 hours after each treatment. The gene expression was analyzed using a microarray system. Cytokines were measured by Bio-plex and, VEGF by ELISA.
Results: All group A patients were responsive to IFX treatment, one patient developed a giant coronary artery lesion (CAL) after IFX. Twenty-nine transcripts showed a change >2.0 fold before and after treatment in both group. The 29 transcripts included the expression of genes related to immune function, including IL1β, Toll-like receptor, and Fc gamma receptor. The 310 transcripts that were only downregulated in group B included intercellular adhesion molecule 1 (ICAM1). Although proinflammatory cytokines and chemokines, including IL6, G-CSF, and MCP-1, were effectively suppressed with IFX , the serum VEGF levels were not significantly suppressed.
Conclusions: The profile of gene expression differed in the patients treated with IFX and IVIG. VEGF, which plays a role in the development of coronary artery lesions, could not be completely blocked with IFX treatment.
- © 2012 by American Heart Association, Inc.