Characterisation of whole-blood extrachromosomal circular DNAs in Kawasaki disease complicated by coronary artery aneurysm.

Abstract

BACKGROUND: Extrachromosomal circular DNAs are critical regulators of stress responses, immunity, and inflammation pathways. However, their role and underlying mechanisms in Kawasaki disease complicated by coronary artery aneurysm remain poorly understood. METHODS: Whole blood samples from six children with Kawasaki disease, including three with coronary artery aneurysm group and three without coronary artery aneurysm (control group), were subjected to extrachromosomal circular DNA sequencing. Putative extrachromosomal circular DNAs were identified using Circle-Map. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on genes associated with upregulated extrachromosomal circular DNAs, and an exploratory immune-signature profiling was performed using the single-sample gene set enrichment analysis algorithm. RESULTS: We identified 4,790 differential extrachromosomal circular DNAs between the coronary artery aneurysm and control groups, of which 4,789 were upregulated in the CAA group. The extrachromosomal circular DNAs in the coronary artery aneurysm group were more concentrated and shorter in length than those in the control group. Upregulated extrachromosomal circular DNAs were mainly derived from autosomes, particularly chromosomes 3, 4, and 7. Functional enrichment analysis indicated that genes associated with upregulated extrachromosomal circular DNAs were mainly involved in response to stimulus-related terms and pathways, including chemokine signalling, cGMP-PKG signalling, and calcium signalling. Immune-signature analysis suggested that the coronary artery aneurysm group exhibited more specific immune responses, whereas the control group tended towards broader immune regulatory processes. CONCLUSIONS: Coronary artery aneurysm and control groups exhibited distinct extrachromosomal circular DNA profiles. These findings suggest that extrachromosomal circular DNA alterations are associated with coronary artery aneurysm in Kawasaki disease and may provide new insights into the molecular features underlying this condition.