Increased soluble ST2 and IL-4 serum levels are associated with disease severity in patients with membranous nephropathy

Abstract

The interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis regulates Th2 reactivity, and ST2 is the receptor for IL-33. In this study, the roles of IL-33 and soluble ST2 (sST2) in the pathogenesis of membranous nephropathy (MN), and their association with disease severity were evaluated. Serum levels of IL-33 and sST2 in 93 patients, and 34 healthy controls (HCs) were measured by enzyme-linked immunosorbent assays. Clinical characteristics were recorded and the estimated glomerular filtration rates (eGFRs) were computed. In addition, the association between serum IL-33 and sST2 levels, and clinical measurements in patients with MN was analyzed. No difference in the serum levels of IL-33 was identified between the patients with MN and HCs. However, the serum levels of sST2 were considerably higher in the MN patients compared with in the HCs at every stage. Higher concentrations of serum IL-2, IL-4, IL-10, IL-17A, and IFN-γ were measured in the MN patients compared with in the HCs. Serum sST2 concentrations were negatively correlated with IL-4 concentrations in the patients with MN. Furthermore, serum sST2 levels were negatively correlated with the eGFRs and serum calcium levels. Serum sST2 levels, but not IL-33 levels, were positively correlated with the 24-h urine protein and serum phosphorus levels. Following treatment, serum sST2 levels were considerably reduced, whereas serum IL-4 and IL-10 levels were significantly increased. These data suggest that sST2 and IL-4, but not IL-33, contribute to the pathogenesis of MN.