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 moie ties attached to IgAl hinge region in IgAl self-aggregation and adhesi on to extracellular matrix (ECM) proteins previously reported in IgA n ephropathy. Serum IgAl samples isolated from healthy individuals were digested with neuraminidase (NA), NA + beta-galactosidase, and NA + be ta-galactosidase + alpha-N-acetylgalactosaminidase to remove the carbo hydrates from the hinge region and were named asialo, agalacto, and na ked IgAl, respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band i ndicating IgAl self-aggregation was clearly observed in asialo, agalac to, and naked IgAl, but not in native IgAl. However, the broad band di sappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgAl adhes ion activities to type IV collagen, fibronectin, and laminin were sign ificantly higher in asialo, agalacto, and naked IgAl than in native Ig Al, using enzyme-linked immunosorbent assay (asialo, agalacto, and nak ed versus native: P < 0.01). In addition, agalacto IgAl had the highes t affinity fur all of the ECM proteins among the deglycosylated IgAl ( agalacto versus asialo and naked, P < 0.05). These results indicated t hat the removal of carbohydrates from the IgAl molecule resulted in no ncovalent self-aggregation and a significant increase in adhesion to t he ECM proteins. It was therefore suggested that the IgAl glycans play ed a protective role against aggregation and adhesion and that the und erglycosylation of the IgAl molecule found in IgA nephropathy could be involved in the nonimmunologic glomerular accumulation of IgAl.