Linkage between IL-23 and coronary arterial lesions in Pediatric Patients with Kawasaki disease

Yi Wei^1,2,3Siqi Feng^1,2,3Jinhui Wu^1,2,3Penghui Yang^1,2,3Ya Su^1,2,3*Qijian Yi^1,2,3*

• ¹Children‘s Hospital of Chongqing Medical University, Chongqing, China
• ²National Clinical Key Cardiovascular Specialty, Chongqing, China
• ³Key Laboratory of Children's Vital Organ Development and Diseases of Chongqing Municipal Health Commission, Chongqing, China

BACKGROUND: Coronary artery lesions (CALs) in Kawasaki disease (KD) are thought to arise from aberrant immune activation and an amplified inflammatory cascade triggered by an unidentified etiologic factor. Interleukin-23 (IL-23)—a pivotal modulator of chronic inflammatory responses and immune-mediated vascular damage—has lately garnered interest regarding its putative role in cardiovascular pathological processes AIM: To explore the correlation between circulating IL-23 concentrations and the occurrence of CALs in pediatric patients with KD. METHODS: Peripheral blood samples were obtained from 103 pediatric patients with KD prior to administration of intravenous immunoglobulin. Using Enzyme-Linked Immunosorbent Assay (ELISA), we quantified circulating cytokine levels in a total of 211 study participants, who were stratified into four distinct cohorts: 47 KD cases with coronary artery lesions, 56 cases without vascular involvement, 58 febrile controls, and 50 healthy controls. RESULTS: Serum IL-23 concentrations were markedly elevated in children with KD [279.69 pg/mL (132.67–693.32)] compared with both febrile controls [161.02 pg/mL (81.50–338.60)] and healthy controls [132.41 pg/mL (61.74–274.28)] (P < 0.001), indicating a disease-specific elevation. Among KD patients, 47 (45.63%) developed CALs. The KD individuals presenting with CAL (KD-CALs) group exhibited markedly higher IL-23 levels [395.76 pg/mL (221.62–1217.19)] compared with KD individuals without CAL (KD-NCALs) [222.81 pg/mL (100.18–388.58), P < 0.001], accompanied by higher Erythrocyte Sedimentation Rate (ESR) and increased Interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), vascular endothelial growth factor (VEGF) levels. IL-23 displayed significant positive associations with multiple inflammatory indices, including white blood cell count (WBC), C-reactive protein (CRP), IL-6, Interleukin-10 (IL-10), Interleukin-17A (IL-17A), MMP-1, and VEGF. Receiver operating characteristic (ROC) analysis showed that IL-23 effectively discriminated KD from controls [area under the curve (AUC)=0.71, cutoff=202.3 pg/mL, sensitivity=66.0%, specificity=68.0%] and KD-CAL from KD-nCAL (AUC=0.69, cutoff=661.2 pg/mL, sensitivity=42.6%, specificity=87.5%). CONCLUSION: Elevated serum IL-23 is associated with heightened inflammatory activity and the presence of coronary artery lesions in KD, suggesting that IL-23 may contribute to CAL pathogenesis and represent a potential biomarker of vascular involvement.