Akademik Veri Yönetim Sistemi
HLA, cilt.91, ss.371, 2018 (SCI-Expanded)
Galactosyltransferase core-1
beta3-galactosyltransferase-1 (C1GALT1) and core 1
3-galactosyltransferase-specific molecular chaperone (COSMC) are required for
the O-glycosylation of the
IgA1 hinge region. IgA nephropathy (IgAN) patients have high serum levels of galactose-deficient
immunoglobulin A1 (GdIgA1). We aimed to demonstrate that hypermethylation of
the COSMC gene promoter region is associated with GdIgA1 levels in IgAN
patients.
Thirty-nine IgAN patients, 11 relative
healthy controls, and 20 normal controls were recruited. Peripheral B lymphocytes
were treated with Interleukin- 4 (IL-4) or 5-Aza-2'-deoksisitidin (AZA), after
which COSMC mRNA levels and the DNA methylation profile of the COSMC gene promoter
region were measured by real-time RT-PCR. The GdIgA1 levels were measured using
ELISA in cell culture supernatant and patient serum.
The levels of DNA methylation were positive correlated with the level of
serum or supernatant Gd-IgA1in the IgAN patients (respectively: r=0.28, p=0.02,
r=0.30, p=0.009). COSMC mRNA levels were found to be negatively correlated with
serum GdIgA1 (r=-0.38, p=0.001). GdIgA1 levels were significantly higher in
IgAN patients compared to healthy controls (serum: p<0.001, supernatant: p=0.004). Supernatant
or serum GdIgA1 levels correlated with clinical parameters such as eGFR (r=-0.34,
p=0.03; r=-0.32, p=0.05, respectively) and serum Creatinine (respectively; r=0.44,
p=0.005; r=0.39, p=0,01), but not with proteinuria and the MEST-C scores.
High levels of GdIgA1 have a high positive
predictive value for diagnostic purposes; however, it is not informative about
disease progression or severity. The epigenetic silencing of the COSMC gene by
hypermethylation of its promoter can be one of the mechanisms responsible for
high GdIgA1 levels in IgAN patients.