Detection of alpha(beta)-N-acetyl-D-galactosamine-binding sites in kidney--relation to Henoch-Schönlein-associated IgA nephropathy.
Henoch-Schönlein purpura is the most common vasculitis of childhood, accompanied by the deposition of IgA1 immunoglobulins into the glomerular mesangium. The actual molecular mechanism of IgA deposition is not clear, but the altered glycosylation of O-linked oligosaccharides of the hinge region of IgA1 is generally considered as the crucial etiopathogenic factor. The oligosaccharides of this glycoprotein from healthy persons are principally of mucin-type Galbeta1,3GalNAcalpha-O-glycan core structure, frequently sialylated. The patient's IgA hinge region saccharide is an incomplete GalNAcalpha-O-glycan only. This study investigates the presence of binding sites for alpha-GalNAc and beta-GalNAc in frozen sections of kidney with and without nephropathy prompted by the possibility for a lectin mechanism of IgA deposition to mesangium. Neoglycoproteins prepared as conjugates with derivatized alpha- or beta-GalNAc moieties as histochemically crucial ligands and biotinylated bovine serum albumin as a carrier were employed for this purpose. The result of the experiments demonstrated expression of specific and accessible binding sites for both alpha- and beta-GalNAc in tubules but not in glomeruli of kidney samples both with and without nephropathy. These findings imply no involvement of a lectin mechanism of IgA1 binding to mesangium, unless a temporary alteration of accessibility of binding sites for probes in glomeruli occurs or the linkage region beyond the monosaccharide is pivotal for a receptor whose binding site may accommodate a peptide epitope in addition to the O-linked alpha-GalNAc residue.
Sedivá
A
A
Institute of Immunology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. anna.sediva@lfmotol.cuni.cz
Stejskal
J
J
Bartůnková
J
J
Smetana
K
K
Gabius
H J
HJ
D000116:Acetylgalactosamine / Q000378:metabolism*; D001665:Binding Sites; D002648:Child; D005629:Frozen Sections; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D011695:IgA Vasculitis / Q000150:complications*; D007070:Immunoglobulin A / Q000737:chemistry* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000737:chemistry / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship
D007070:Immunoglobulin A; D000116:Acetylgalactosamine