IL1R2 identified as a key hub gene regulating vascular endothelial function in Kawasaki disease

Kawasaki disease (KD) is a multisystemic vasculitis of unknown aetiology in children. KD with coronary artery lesion (CAL) is now the leading acquired heart disease in children. Peripheral blood mononuclear cells (PBMCs) play roles in KD. We identified hub genes based on RNA sequencing data and validated them in PBMCs and human umbilical vein endothelial cells (HUVECs) co-culture with PBMCs. Expression profiling by high throughput sequencing (RNA-seq data) PBMCs from 12 acute KD patients and 12 healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). We selected 20 KD with CAL, 20 KD patients without CAL and 40 healthy controls for validation, and established HUVECs co-culture with PBMCs. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from PBMC-HUVECs co-cultures. A total of 6039 DE-mRNAs were found (2267 upregulated, 3772 downregulated). Thirty hub genes were selected. KD PBMCs significantly impaired HUVECs viability and migration. IL1R2 was downregulated, FCGR1A, and CD177 mRNAs were upregulated in acute KD and KD with CAL. IL1R2 was elevated, FCGR1A and CD177 mRNAs were downregulated in convalescence and KD without CAL. And the real-time PCR and ELISA results showed IL1R2 was downregulated in acute KD PBMC-HUVECs co-cultures and elevated in convalescence. These findings may improve our understanding of PBMCs and PBMC-HUVECs co-cultures with PBMCs in KD.