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 an d predominant mesangial IgA deposits of polymeric nature. The abnormal glyc osylation of the carbohydrate moieties in the hinge region of the IgA molec ule has recently attracted much attention. In this study we investigated th e galactosylation and sialylation of monomeric and polymeric IgA, isolated from patients with IgAN. Total IgA, in serum samples from patients with IgA N or from healthy controls was isolated with a jacalin-agarose column as ja calin-bound protein (JBP). Monomeric and polymeric IgA, were distinctly sep arated by fast protein liquid chromatography, Lectin binding assays were de signed 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 w ith results in healthy control subjects. However, a reduction in terminal g alactosylation was not found in polymeric IgA, isolated from patients with IgAN. Instead, increased sialylation of IgA(1) (alpha 2-3 linked to galacto se) was demonstrated in polymeric IgA(1), This abnormality of IgA, could be ar considerable implication on the pathogenesis of IgAN, because the maskin g effect of sialic acid may hinder the clearance of polymeric IgA, by the a sialoglycoprotein receptor (ASGP-R) of the liver cells. An increase in the sialylated content would also render the polymeric IgA from patients with I gAN more anionic, These immunochemical properties may contribute to the sel ective glomerular deposition of polymeric IgA(1) in IgAN.