Lysophosphatidylcholine as a Novel Diagnostic Biomarker in Kawasaki Disease: Based on Immunometabolism-Related Signature.

Purpose: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Delayed diagnosis and treatment elevate the risk of coronary artery complications. This study aims to investigate metabolic disorders associated with its potential pathophysiology and to explore novel diagnostic biomarkers. Patients and Methods: Untargeted metabolomics was used to identify significantly dysregulated metabolic pathways in patients with KD. Targeted lipidomic analysis was performed to detect differentially expressed lipid metabolites. Candidate plasma biomarkers were quantified using ELISA. Single-cell RNA sequencing was used to analyze the expression of lipid metabolism-related genes and cellular heterogeneity. Results: Sphingolipid metabolism was confirmed to be dysregulated in patients with KD. Twelve differentially expressed lipid species were identified: 20:5-carnitine, sphingomyelin 32:2;O2, ceramide d16:0/24:0, glucosylceramide d18:1/26:0, lysophosphatidylcholine (LPC) O-16:0, LPC 17:0, LPC 18:0, and phosphatidylcholine (PC) 32:2, PC 36:3, PC 40:3, PC 40:4, and PC 40:7. ELISA validation confirmed the lipidomics-identified alterations in LPC. As a diagnostic biomarker, LPC achieved an area under the curve (AUC) of 0.768, with 64.7% sensitivity and 88.2% specificity. Single-cell RNA sequencing data revealed a marked accumulation of monocytes in KD, along with upregulated expression of lipid metabolism-associated genes. Notably, the expression levels of inflammatory genes were altered along with those of LPC degradation-related genes in monocytes from patients with KD. Conclusion: This study demonstrated significant dysregulation of lipid metabolism in KD, potentially driven by inflammatory responses in monocytes. LPC has emerged as a potential biomarker of KD and provides new insights into its early diagnosis.