| Research Abstract |
We investigated the relationship between O-glycans in IgAl hinge and the IgA nephropathy (IgAN) supported by the Grand, and have suggested the following points.
1. Structural analyses of O-glycan structure in the hinge region of serum IgAl in IgAN.
(1) Increase of serum IgAl having hypoglycosylated O-glycans (underglycosylated IgAl) was found in IgA N (2000).
2. Glomerular deposition of underglycosylated IgAl.
(1) Undeglycosylated IgAl tended to self-aggregate.
(2) The IgAl fraction that could accumulate in rat glomeruli was isolated and investigated. The O-glycans in the IgAl fraction was hypoglycosylated (1999). Furthermore, enzymatically deglycosylated IgAl accumulated and induced inflammatory cell reaction in rat glomeruli (2002).
(3) Analysis using matrix assisted laser desorption/ionization timc-of-flight mass spectrometry (MALDI-TOFMS) showed that 0-glycan of IgAl deposited in glomeruli in IgAN was also underglycosylated (200l).
(4) Underglycosylated IgAl could bind to IgG3 subclass and complement C3 (2002).
(5) IgG antibody against synthetic hinge peptide was investigated. Increase and epitope specificity of IgG antibody activity were detected in the patients with IgAN (1999, 2002).
3. Origin of underglycosylated IgAl and its biological activity toward glomerular injury.
(1) Asialo-, agalacto-hinge glycopetides in tonsillar IgAl were increased in IgAN (2002).
(2) Comprehensive gene expression of mesangial cells stimulated by asialo-, agalacto-IgAl was attempted using cDNA array, revealing the difference between the IgAl and native IgAl (2002).
From these investigations supported by the Grand, it was found that underglycosylated IgAl played a role in the pathogenesis and progression of IgAN, and the underglycosylated IgAl was originated from tonsils in at least some of IgAN patients.
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