Identification and clinical validation of immune-related genes as potential diagnostic and therapeutic targets in Kawasaki disease

Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology, involving immune-related pathways and genes. This study aimed to identify immune-related differentially expressed genes (IR-DEGs) during the acute phase of KD and explore potential diagnostic and therapeutic targets. Three datasets were applied in this work, including GSE18606, GSE68004, and GSE63881. IR-DEGs were obtained from GSE18606 and ImmPort database. GO and KEGG analyses were performed on IR-DEGs. The expression levels of hub genes with an area under the curve (AUC) greater than 0.9 were evaluated using the external datasets and were investigated with the acute phase of KD. Molecular docking was employed to investigate the potential of these hub genes as drug targets. Four hub genes (CAMP, MMP9, S100A9, and S100A12) associated with immune were identified, which were confirmed by datasets GSE68004, GSE63881, and clinical experimental data. In the infiltration abundance of KD, B cells memory, T cells CD4 naïve, T cells CD4 memory activated, monocytes, mast cells activated, and neutrophils in the two groups were significantly different. Immune cell infiltration analysis further revealed that neutrophil was positively correlated with these four hub genes. Methotrexate and curcumin exhibit strong affinity for S100A12 and MMP9, indicating that these two drugs may modulate the inflammatory response in KD via S100A12 or MMP9. This study provides valuable biomarkers and treatment insights into KD, offering new perspectives for clinical management and prognosis.