Increased sialylation of polymeric immunoglobulin A1:: Mechanism of selective glomerular deposition in immunoglobulin A nephropathy?

Immunoglobulin A nephropathy (IgAN) is characterized by raised serum IgA and predominant mesangial IgA deposits of polymeric nature. The abnormal glycosylation of the carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this study we investigated the galactosylation and sialylation of monomeric and polymeric IgA, isolated from patients with IgAN. Total IgA, in serum samples from patients with IgAN or from healthy controls was isolated with a jacalin-agarose column as jacalin-bound protein (JBP). Monomeric and polymeric IgA, were distinctly separated by fast protein liquid chromatography, Lectin binding assays were designed to examine the sialylation and the expression of terminal galactose and N-acetyl galactosamine of the O-linked carbohydrate in the hinge region of the IgA molecule. Reduced terminal galactosylation was demonstrated in serum IgA and monomeric IgA, isolated from patients with IgAN as compared with results in healthy control subjects. However, a reduction in terminal galactosylation was not found in polymeric IgA, isolated from patients with IgAN. Instead, increased sialylation of IgA(1) (alpha 2-3 linked to galactose) was demonstrated in polymeric IgA(1), This abnormality of IgA, could bear considerable implication on the pathogenesis of IgAN, because the masking effect of sialic acid may hinder the clearance of polymeric IgA, by the asialoglycoprotein receptor (ASGP-R) of the liver cells. An increase in the sialylated content would also render the polymeric IgA from patients with IgAN more anionic, These immunochemical properties may contribute to the selective glomerular deposition of polymeric IgA(1) in IgAN.