Epigenome-Wide DNA Methylation Profiling of Peripheral Blood Shows Lymphocyte Dysfunction in Children with Kawasaki Disease

Abstract

Kawasaki disease (KD) is an acute childhood vasculitis, commonly seen in children under the age of five. Despite extensive research over the past five decades, the pathogenesis of KD remains elusive. The objective of this epigenetic reanalysis study is to delineate common pathways involved in KD using a bioinformatics approach. Array datasets from the Gene Expression Omnibus repository were extracted and subjected to analysis using the Chip Analysis Methylation Pipeline in the R statistical tool for the identification of differential methylation probes and differential methylation regions. Adaptive immune genes CD8B, RAG1, IL-7R, STAT1, and CCR7 were significantly hypermethylated in acute KD as compared to healthy controls. Gene enrichment analysis showed that genes involved in T-cell receptor activation and differentiation, antigen processing and presentation of MHC class I were hypermethylated, whereas neutrophil degranulation was hypomethylated in the acute phase of KD as compared to healthy controls. The proportion of neutrophils significantly increased, while the proportions of CD4 T-cells and CD8 T-cells decreased in the peripheral blood of children with acute KD as compared to healthy controls. Reduced proportions of CD4 T cells and CD8 T cells, as well as hypermethylation of their genes, have been observed in the peripheral blood of patients with acute KD.