Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins

The aim of this study was to investigate the role of carbohydrate moieties attached to IgA 1 hinge region in IgA 1 self-aggregation and adhesion to extracellular matrix (ECM) proteins previously reported in IgA nephropathy. Serum IgAI samples isolated from healthy individuals were digested with neuraminidase (NA), NA + f3-galactosidase, and NA + 13-ga- lactosidase + a-N-acetylgalactosaminidase to remove the car- bohydrates from the hinge region and were named asialo, agalacto, and naked IgA I , respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band indicating IgA I self-aggrega- tion was clearly observed in asiabo, agalacto, and naked IgA I, but not in native IgA I. However, the broad band disappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgAb adhesion activities to type IV collagen, fibronectin, and laminin were significantly higher in asiabo, agalacto, and naked IgAl than in native IgA1, using enzyme-linked immunosor- bent assay (asiabo, agalacto, and naked versus native: P < 0.0 1). In addition, agalacto IgA 1 had the highest affinity for all of the ECM proteins among the deglycosybated IgA I (agalacto versus asiabo and naked, P < 0.05). These results indicated that the removal of carbohydrates from the IgA I molecule resulted in noncovalent self-aggregation and a significant increase in adhesion to the ECM proteins. It was therefore suggested that the IgAl glycans played a protective role against aggregation and adhesion and that the underglycosylation of the IgA I molecule found in IgA nephropathy could be involved in the nonimmunobogic gbomerular accumulation of IgA I.