Illuminating the enigmatic pathogenesis of Kawasaki disease: Unveiling novel therapeutic avenues by targeting FCGR3B-S100A12 pathway.

Kawasaki disease (KD) primarily affects the pediatric population and exhibits a notable incidence of drug resistance, resulting in coronary artery damage and thrombosis. This study aimed to identify innovative therapeutic targets for KD treatment. By harnessing single-cell data derived from peripheral blood mononuclear cells, we identified differentially expressed genes. Through the integration of eQTL data and Mendelian randomization analysis, we identified FCGR3B and S100A12 were causally linked to KD. The DrugBank database showed their potential as drug target candidates. GSEA further elucidated their roles on coronary artery damage and thrombosis. Furthermore, we have confirmed that the ligand-FCGR3B complex enhances the intracellular calcium concentration (Ca2+) within the cytoplasm, which in turn accelerates the secretion of S100A12, a pro-inflammatory cytokine that targets endothelial cells, from neutrophils. By integrating existing research, we proposed a synergistic effect that FCGR3B-S100A12 pathway positively modulates the development of coronary artery damage and thrombus formation, suggesting their perspectives in clinical treatment.