COSMC expression as a predictor of remission in IgA nephropathy

Abstract

Purpose The impact of core 1,3-galactosyltransferase-specific molecular chaperon (COSMC) gene expression and methylation profile on clinical progression of IgA nephropathy (IgAN) is unclear. The aim of this study was to determine the clinical significance and the relation of the COSMC gene expression and methylation pattern with the progression of IgAN. Methods Thirty-nine biopsy-confirmed IgAN patients, 11 healthy relatives and 20 healthy controls were recruited. The COSMC mRNA levels and methylation profile of COSMC gene promoter were measured using the quantitative real-time PCR. The galactose-deficient IgA1 (Gd-IgA1) levels were measured using ELISA in serum and cell culture supernatant. The effect of IL-4 and AZA on COSMC expression and methylation and the correlation of COSMC gene expression and methylation levels with baseline kidney function tests, histology and long-term outcomes were examined. Results The mean COSMC mRNA level was significantly lower, and serum Gd-IgA1 level was higher in IgAN patients compared with the control groups (p < 0.001, and p = < 0.001, respectively). The COSMC mRNA levels were correlated with intensity of hematuria (r = - 0.41, p = 0.009), serum creatinine level (r = - 0.37, p = 0.002) and eGFR (r = 0.36, p = 0.002). The COSMC methylation levels were correlated with age (r = 0.25, p = 0.04) and baseline eGFR (r = - 0.326, p = 0.006). Twenty IgAN patients (51.3%) reached to complete (5, 12.8%) or partial remission (15, 38.5%) after a median of 34.5 months (IQR, 13.75-71). In multivariable Cox regression analysis, COSMC mRNA expression (adjusted HR (aHR) 1.871, 95% CI 1.287-2.722, p = 0.001) and Oxford T score (aHR 0.355, 95% CI 0.146-0.859, p = 0.022) predicted the remission. Conclusion COSMC mRNA level is a novel biomarker candidate to predict the remission in IgAN patients.