The Plasma Level Of Soluble Il-2 Receptor (Sil-2r) Is Elevated In Children With Acute Kawasaki Disease

Purpose: Kawasaki disease (KD) is a systemic vasculitis syndrome caused by immune dysfunction involving regulatory T cells (Tregs). Circulating soluble interleukin 2 receptor (sIL-2R) has been shown to regulate T-lymphocyte activation in various immunological disorders. To investigate the effect of plasma sIL-2R on Tregs, we analyzed the relationship between sIL-2R, Tregs and the IL-2/STAT5 signaling pathway in children with KD. Methods: Blood samples were collected from 33 children with KD before and after intravenous immunoglobulin therapy, as well as from 14 age-matched healthy controls. Circulating levels of CD4(+)CD25(+)Foxp3(+) Tregs, levels of phosphorylated-STAT5 (pSTAT5), and IL-2R in CD4(+)CD25(+)Foxp3(+) Tregs, and the levels of sIL-2R and IL-2 family cytokines in plasma were measured by flow cytometry, cytometric bead array and Real-time PCR, respectively. Results: The proportion of Tregs, mRNA levels of associated factors (Foxp3, GITR, CTLA-4 IL-2R alpha and IL-2R beta), and protein levels of pSTAT5 in Tregs were significantly reduced (P < 0.01), while plasma sIL-2R concentrations were significantly increased in acute KD (P < 0.01). Moreover, circulating sIL-2R levels were higher in KD patients with coronary artery lesions (KD-CAL(+)) than those without coronary artery lesions (KD-CAL(-)) (P < 0.01). Plasma sIL-2R levels were negatively correlated with expression of IL-2R beta, Foxp3 mRNA and pSTAT5 protein (P < 0.01). Moreover, pSTAT5 protein expression was found to positively correlate with Foxp3 mRNA expression (P < 0.01). Intravenous immunoglobulin (IVIG) treatment effectively eliminated these differences between patients and controls. Conclusion: Aberrant signaling of the IL-2/STAT5 pathway may be mediated by increased sIL-2R and may contribute to downregulation of Tregs in KD patients.