Identification and mechanistic elucidation of neutrophil migration-related biomarkers in Kawasaki disease based on single-cell and transcriptome sequencing

Kawasaki Disease (KD), an acute pediatric vasculitis, predominantly impacts children under the age of five. It stands as the primary etiology of acquired coronary artery lesions. Despite being acknowledged as a systemic inflammatory disorder, the pathogenesis of KD remains unclear, while it exhibits a strong correlation with the activation and dysregulation of innate immune cells. This research aims to explore its mechanisms at the cellular and molecular levels and construct a diagnostic model. Single-cell RNA sequencing datasets (GSE254657) and microarray datasets (GSE73461, GSE68004) were obtained from the GEO database. Single-cell data were processed, annotated, and analyzed for differential abundance using various software packages and algorithms, such as Seurat and harmony. Differential expression analysis, enrichment analysis, functional annotation, and migration activity assessment were performed. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify relevant genes. Diagnostic models were constructed and validated through univariate, LASSO, and multivariate logistic regression analyses. The molecular mechanisms of biomarkers were explored using multiple databases. In Kawasaki disease (KD) blood, the abundance of neutrophils, megakaryocytes, and plasmacytoid dendritic cells was significantly up—regulated. Neutrophils were classified into nine subtypes, among which the neutro7 subtype exhibited the highest activation of migration mechanisms. Five candidate genes associated with neutrophil migration were identified, and four biomarkers (PIM3, S100A12, S100A9, SOCS3) were selected for the construction of a diagnostic model. This model manifested high diagnostic capacity, reliability, and clinical decision—making value in both the training and validation cohorts. The molecular mechanisms and regulatory networks of the biomarkers were elucidated. This research explored the neutrophil-related pathogenesis of Kawasaki disease (KD) and established a diagnostic model with favorable performance, offering novel theoretical evidence and potential targets for comprehending the pathogenesis of KD. Identified genetic features serveras an exploratoryframework for future diagnostic advances, offering potentialdiagnostic relevance in detecting subtypes such as incompleteKawasaki disease that are difficult to diagnoserearly. However, validation through large-scale prospective cohort studies is still required. Furthermore, distinctions from other inflammatory diseases also need further confirmation.