Circulating miR-10b-5p drives Kawasaki vasculitis via endothelial reprogramming and nominates CXCL8 as an early diagnostic biomarker

Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children, yet no specific biomarker enables early diagnosis at emergency department presentation. We aimed to define the molecular mechanisms driving KD vasculitis and to identify a clinically actionable early diagnostic marker. Whole microRNA sequencing of buffy coat specimens from patients with KD and febrile controls identified 68 upregulated microRNAs, of which 13 were prioritized. Candidates were validated in two KD-like vasculitis mouse models, and miR-10b-5p was consistently elevated. Inhibition of miR-10b-5p by a miRCURY locked nucleic acid inhibitor attenuated aortic root inflammation in vivo. In human coronary artery endothelial cells from adult donors, miR-10b-5p directly suppressed marker of proliferation Ki-67 ( MKI67 ) and chromobox 5 ( CBX5 ), driving a transition from proliferative and metabolic programs toward a proinflammatory phenotype, as confirmed by single-cell and bulk RNA sequencing. Chromatin accessibility profiling revealed increased accessibility at the C-X-C motif chemokine ligand 8 ( CXCL8 ) promoter, and motif analysis identified CCAAT enhancer binding protein alpha ( CEBPA ) as the key transcriptional activator; CEBPA knockdown abrogated miR-10b-5p-induced CXCL8 upregulation, and direct binding was confirmed by binding assays and chromatin immunoprecipitation. Serum CXCL8 was markedly elevated in patients with KD relative to febrile controls at first presentation before definitive diagnosis and declined significantly at the 8-week follow-up. Receiver operating characteristic analysis demonstrated diagnostic utility, with sensitivity and specificity of 83.3% at an optimal cut-off of 20.91 pg/ml. In conclusion, we define a miR-10b-5p– MKI67 / CBX5 –CEBPA–CXCL8 axis driving endothelial reprogramming and neutrophil-recruiting inflammation in KD and identify serum CXCL8 as a candidate biomarker for timely KD recognition.