Abstract 32: Improper Histone Modification Of Gene Expression In Kawasaki Disease May Influence Both Its Development And Outcome

Abstract

Kawasaki disease (KD) is characterized by development of an autoimmune vasculitis and potential coronary artery lesions (CAL). Patients present with significantly marked expression of various immune cells and the inflammatory cells that they produce, recruit, or secrete, particularly cytokines. Concurrently, regulatory immune cells that suppress immune and inflammatory cells are significantly reduced in KD, particularly regulatory T cells (Tregs) such as CD4+CD25+FOXP3+ Tregs. Therefore, the clinical picture results from an unchecked, marked increase of immune and inflammatory cells infiltrating passed activated endothelial cells and into the vascular wall. This appears to largely be a consequence of amplified cell signaling via the Ca2+/NFAT pathway in KD, which is involved in targeted gene expression. As a result, we hypothesized that epigenetic control of gene expression through histone modifications may play a leading role in development of KD, its complications, and recovery. A previous study found significant DNA hypomethylation of CpG sites for the SOCS1 gene in KD patients (n=32), which was higher in patients without CAL. We conducted a preliminary study to widely examine epigenetic changes in DNA methylation of CpG sites before and after IVIG treatment in KD patients (n=9) using age-matched febrile controls (n=8). Our results demonstrated ≥10% differences in DNA methylation rates for 67 genes in KD patients, in addition to 10 genes with ≥15% methylation difference. Larger studies are required to accurately determine the role of epigenomic changes in KD development, in addition to investigations of the methylation reactions which regulate them (see Figure 1).