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

Impaired core I β3-Gal-T-specific molecular chaperone (Cosmc) expression-caused IgA1 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. IgA1 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 IgA1 O-glycosylation level.

Cosmc mRNA expression and IgA1 O-glycosylation level in IgAN patients were significantly lower than normal controls. Treatment of LPS could obviously inhibit the Cosmc expression and increase the IgA1 secretion in peripheral lymphocytes of IgAN patients, which resulted in a significantly increase in IgA1 aberrant glycosylation level. Addition of MPA could significantly increase the Cosmc expression level along with a decrease in IgA1 secretion, leading to a reverse of aberrant glycosylation. A significant positive correlation between the Cosmc expression and IgA1 O-glycosylation level was noticed.

MPA can up-regulate the Cosmc expression and reverse the IgA1 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.