|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 2003 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 2002 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Immunoglobulin G is a glycoprotein containing biantennary complex-type oligosaccharides. A significant increase in the proportion of IgG lacking galactose has been observed in MRL/lpr mice, which spontaneously develop glomerulonephritis, in which IgG3 cryoglobulin formation correlates with the development of the disease. In the present study, to explore directly the possible relation between the pathogenic potential of IgG cryoglobulin and their patterns of glycosylation, various IgG3 monoclonal antibodies generated from murine cryoglobulin. It was found that a remarkable difference in the renal pathogenicity of two murine IgG3 monoclonal cryoglobulins, identical in the amino acid sequence of their heavy and light chains, but different in galactosylation pattern of the oligosaccharide side chains because of the synthesis in different myeloma cells. Five molecular mutants of a ciyogenic IgG3 monoclonal rheumatoid factor were generated and then the relationship between cryoglobulin activ
ity and oligosaccharide structure of IgG3 mAbs was analyzed. As a result, it was found that the cryoglobulin activity of the mAbs is associated with the galactosylation levels of the oligosaccharide chains. These observations directly demonstrate the role of IgG galactosylation in the pathogenic potential of cryoglobulins.
Next, to investgate a relationship between IgG oligosaccharide and human nephropathy, I analyzed ligosaccharide structures of IgG from patients with membranous nephropathy and diabetic nephropathy, which show IgG deposit in glomeruli, patients with IgA nephropathy, which shows IgA deposit in glomeruli, and healthy individuals. Significant differences in IgG oligosaccharide structures were not found between patients with IgA nephropathy and healthy individuals. In contrast, IgG from patients with membranous nephropathy and those with diabetic nephropathy contained aberrant oligosaccharides which were not detected in IgG from healthy individuals. These results suggest that oligosaccharide moiety of IgG might participate in the development of nephropathy. Less