title: Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins.
abstract: The aim of this study was to investigate the role of carbohydrate moieties attached to IgA1 hinge region in IgA1 self-aggregation and adhesion to extracellular matrix (ECM) proteins previously reported in IgA nephropathy. Serum IgA1 samples isolated from healthy individuals were digested with neuraminidase (NA), NA + beta-galactosidase, and NA + beta-galactosidase + alpha-N-acetylgalactosaminidase to remove the carbohydrates from the hinge region and were named asialo, agalacto, and naked IgA1, respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band indicating IgA1 self-aggregation was clearly observed in asialo, agalacto, and naked IgA1, but not in native IgA1. However, the broad band disappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgA1 adhesion activities to type IV collagen, fibronectin, and laminin were significantly higher in asialo, agalacto, and naked IgA1 than in native IgA1, using enzyme-linked immunosorbent assay (asialo, agalacto, and naked versus native: P < 0.01). In addition, agalacto IgA1 had the highest affinity for all of the ECM proteins among the deglycosylated IgA1 (agalacto versus asialo and naked, P < 0.05). These results indicated that the removal of carbohydrates from the IgA1 molecule resulted in noncovalent self-aggregation and a significant increase in adhesion to the ECM proteins. It was therefore suggested that the IgA1 glycans played a protective role against aggregation and adhesion and that the underglycosylation of the IgA1 molecule found in IgA nephropathy could be involved in the nonimmunologic glomerular accumulation of IgA1.
authors.affiliation: Department of Medicine, School of Medicine and Nursing, Kitasato University, Sagamihara-City, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kokubo
authors.forename: Y
authors.initials: Y
authors.lastname: Hiki
authors.forename: H
authors.initials: H
authors.lastname: Iwase
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Toma
authors.forename: K
authors.initials: K
authors.lastname: Hotta
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism / Q000502:physiology*; D011134:Polysaccharides / Q000378:metabolism / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D007070:Immunoglobulin A; D011134:Polysaccharides