title: Defective immunoglobulin A (IgA) glycosylation and IgA deposits in patients with IgA nephropathy.
abstract: Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan-specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N-acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α-2,6-sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.
authors: Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland.
authors: Ragnhildur
authors: R
authors: Kolka
authors: Helgi
authors: H
authors: Valdimarsson
authors: Magnus
authors: M
authors: Bodvarsson
authors: Sverrir
authors: S
authors: Hardarson
authors: Thorbjorn
authors: T
authors: Jonsson
mesh_terms: D000116:Acetylgalactosamine / Q000097:blood / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D037102:Lectins; D008297:Male; D008875:Middle Aged; D012799:Sialyltransferases / Q000097:blood / Q000276:immunology; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D037102:Lectins; D012799:Sialyltransferases; D000116:Acetylgalactosamine; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: Immunoglobulin A nephropathy; O-glycosylation; immunoglobulin A; immunoglobulin A immune complexes