Molecular characterization of Kawasaki disease subgroups using cell-free RNA profiling.

Kawasaki disease is a pediatric vasculitis and the leading cause of acquired heart disease in children. The heterogeneous clinical presentation of Kawasaki disease complicates diagnosis and treatment, highlighting the need for molecular signatures to stratify patients into subgroups to better understand pathogenesis. We performed plasma cell-free RNA sequencing on samples from 98 patients diagnosed with Kawasaki disease, 86 febrile children (62 viral infection, 24 bacterial infection), and 5 healthy children. The Kawasaki disease patients were previously classified into one of four clinical subgroups using 14 clinical variables. Significant differences were observed in cell-free RNA transcript abundance, pathway enrichment scores, and cell type-of-origin fractions, including differences in hepatocyte injury, mitochondrial dysfunction, platelet activation, and developmental markers. This study demonstrates the utility of cell-free RNA to characterize Kawasaki disease subgroups at a molecular level. Cell-free RNA profiles may be used as biomarkers for Kawasaki disease stratification and offer new insight into the pathogenesis of specific KD phenotypes.