Profile of Urinary Cytokines in Kawasaki Disease: Non-Invasive Markers

Abstract

This cohort study aimed to investigate urinary cytokines expression to help identify a less invasive method of cytokine detection for Kawasaki disease (KD). Patients with confirmed KD were recruited. Patients with fever or urinary tract infection (UTI) were enrolled as control groups. Urinary samples were collected before and 3 days after intravenous immunoglobulin (IVIG) treatment. The levels of cytokines were detected by MILLPLEX® MAP human multiplex assay. All cytokines, i.e., epidermal growth factor (EGF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-13, IL-17A, IL-33, interferon-gamma-induced protein (IP)-10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) except monocyte chemoattractant protein (MCP)-1 were significantly higher in the KD group, compared with the fever-control (FC) group, whereas the expressions of IFN-γ, IL-1β, IL-6, IL-8, IL-17A, IL-33, MCP-1, MIP-1β, and TNF-α were significantly lower in the urine of KD patients, as compared with the UTI group. The expressions of EGF, IFN-γ, IL-8, IL-13, and IL-17A were higher in the urine of KD patients than in the FC group, whereas the level of IL-1β was lower in KD than in the UTI group after age adjustment by logistic regression. Levels of IL-6, IL-8, IL-13, IP-10, and MCP-1 were significantly higher in the pre-IVIG urine of KD patients than in the post-IVIG treatment group. Additionally, urine IL-4 and blood C-reactive protein were higher in the KD group with coronary artery lesion (CAL) than in the non-CAL group. Results of this study provide a new view of urinary cytokine expression in the disease progress of KD, which may help clinicians to predict and prevent morbidity early and non-invasively.