MFG-E8 in Kawasaki Disease: Role in Endothelial Injury and Diagnostic Potential.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis predominantly affecting children under five years old, with coronary artery lesions (CALs) being a severe complication. Despite the effectiveness of intravenous immunoglobulin (IVIG) therapy, a subset of patients remains unresponsive, necessitating alternative strategies. Milk Fat Globule Epidermal Growth Factor 8 (MFG-E8) is a secreted glycoprotein that functions as a bridge between damaged cells and phagocytes, conferring the ability to regulate immunity and inflammation. This study aimed to investigate the potential role of MFG-E8 in KD pathogenesis. METHODS: Serum levels of MFG-E8 were measured via ELISA. CAWS was utilized to induce a murine model of coronary vasculitis, with MFG-E8 being administered intraperitoneally for treatment. Histological evaluation was conducted using H&E and IHC staining. Serum-stimulated THP-1 cells were co-cultured with endothelial cells to establish an inflammatory environment in vitro, with exogenous supplementation of MFG-E8. Pyroptosis-related markers were assessed by Western blot or immunofluorescence staining. Oxidative stress-related indicators were measured using commercially available assay kits. RESULTS: Serum MFG-E8 levels were significantly lower in KD patients, especially those with CALs, compared to febrile and healthy controls. ROC analysis showed that combining MFG-E8 with Fbg and TT improved the ability to distinguish KD from other febrile illnesses. Further analyses displayed negative correlations between MFG-E8 and parameters pointing to inflammation. In the murine model of vasculitis, MFG-E8 supplementation alleviated coronary artery inflammation, reduced endothelial cell pyroptosis, and mitigated oxidative stress. Similar results were presented in vitro experiments using KD serum-treated endothelial cells. CONCLUSION: MFG-E8 represents a potential biomarker for the diagnosis of KD and exhibits protective effects against endothelial cell injury during the acute phase.