Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy

Impaired core I beta 3-Gal-T-specific molecular chaperone (Cosmc) expression-caused IgA(1) aberrant O-glycosylation is one of the main pathogeneses of IgA nephropathy (IgAN).This study tried to elucidate whether mycophenolic acid (MPA) could up-regulate Cosmc expression of peripheral lymphocytes in IgAN patients and reverse the dys-O-glycosylation. Peripheral lymphocytes of eighteen IgAN patients and twelve normal controls were isolated and cultured for 3-7 days with or without lipopolysaccharide (LPS) and MPA. Cosmc mRNA and protein expression levels were measured by real-time RT-PCR and western blot. IgA(1) and O-glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding test. Correlation analysis was performed between Cosmc expression levels and IgA(1) O-glycosylation level. Cosmc mRNA expression and IgA(1) O-glycosylation level in IgAN patients were significantly lower than normal controls. Treatment of LPS could obviously inhibit the Cosmc expression and increase the IgA(1) secretion in peripheral lymphocytes of IgAN patients, which resulted in a significantly increase in IgA(1) aberrant glycosylation level. Addition of MPA could significantly increase the Cosmc expression level along with a decrease in IgA(1) secretion, leading to a reverse of aberrant glycosylation. A significant positive correlation between the Cosmc expression and IgA(1) O-glycosylation level was noticed. MPA can up-regulate the Cosmc expression and reverse the IgA(1) aberrant O-glycosylation level in peripheral lymphocytes of IgAN patients, which might be the underlying mechanism of mycophenolate mofetil (MMF) therapy used in treating IgAN.