| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Abnormalities of IgA including underglycosylatlon and polymeric WA immune complex (IC) formation are discussed in the pathogenesis of IgA nephropathy (IgAN), but the pathogenesis of this disease still remains unclear. Since upper respiratory infection exercerbates IgAN and tonsillectomy has therapeutic effects on this disease, the previous studies have examined the pathological role of antigens in this disease. However, definitive antigens that form nephritogenic IgAIC have not been identified. To examine whether specific exogenous antigens are involved in IgAIC formation, we analyzed IgA binding protein (BP) from IgAN patients serum by Mass Spectrometry (MS). After isolation of IgA1/IgA1-BP by jacalin, we performed one-dimensional (1D) electrophoresis and analyzed all bands stained with silver. When we compared 6 IgAN patients with 5 healthy volunteers, both groups identified apolipoprotein, immunoglobulin (Ig) heavy chain(α. Μ, γ) and light chain, Ig J chain, fibronectin (FN), Clinhibitor (C1INH), C4 binding protein(C4bp) and α1microglobulin (MG)as IgAl/IgAI-BP by MS. C4bp was frequently observed in the patients group. Moreover, samples before and after the therapies were analyzed by two dimensional difference gel electrophoresis (2D DIGE) system, but we could not identify new protein more than 1D electrophoresis. We further performed Western blot analysis to compare before and after the therapy in patients and healthy volunteers. Contents of IgAl binding C4bp, IgG, and C3 in IgAN patients were higher than those in the volunteers and decreased after the therapy. Although we could not detect exogenous antigen in IgAl-BP, the present findings suggested that IgG, C4bp and C3 in nephritogenic IC might play a key role in the pathogenesis of this disease.
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