Linkage between IL-23 and coronary arterial lesions in pediatric patients with Kawasaki disease

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.

To explore the correlation between circulating IL-23 concentrations and the occurrence of CALs in pediatric patients with KD.

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.

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 (221.62-1,217.19)] 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%).

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.