Detection of alpha(beta)-N-acetyl-D-galactosamine-binding sites in kidney - Relation to Henoch-Schonlein-Associated IgA nephropathy

Henoch-Schonlein purpura is the most common vasculitis of childhood, accomp anied by the deposition of IgA1 immunoglobulins into the glomerular mesangi um. The actual molecular mechanism of IgA deposition is not clear, but the altered glycosylation of O-linked oligosaccharides of the hinge region of I gA1 is generally considered as the crucial etiopathogenic factor. The oligo saccharides of this glycoprotein from healthy persons are principally of mu cin-type Gal beta 1,3GalNAc alpha-O-glycan core structure, frequently sialy lated, The patient's IgA hinge region saccharide is an incomplete GalNAc al pha-O-glycan only. This study investigates the presence of binding sites fo r alpha-GalNAc and beta-GalNAc in frozen sections of kidney with and withou t nephropathy prompted by the possibility for a lectin mechanism of IgA dep osition to mesangium. Neoglycoproteins prepared as conjugates with derivati zed alpha- or beta-GalNAc moieties as histochemically crucial ligands and b iotinylated bovine serum albumin as a carrier were employed for this purpos e. The result of the experiments demonstrated expression of specific and ac cessible binding sites for both alpha- and beta-GalNAc in tubules but not i n glomerules of kidney samples both with and without nephropathy. These fin dings imply no involvement of a lectin mechanism of IgA1 binding to mesangi um, unless a temporary alteration of accessibility of binding sites for pro bes in glomerules occurs or the linkage region beyond the monosaccharide is pivotal for a receptor whose binding site may accommodate a peptide epitop e in addition to the O-linked alpha-GalNAc residue.