| Project/Area Number |
16590774
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
YAMAGATA Kunihiro (2005) University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor of Medicine, 大学院・人間総合科学研究科, 助教授 (90312850)
小山 哲夫 (2004) 筑波大学, 大学院・人間総合科学研究科, 教授 (80111384)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAYAMA Kouichi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor of Medicine, 大学院・人間総合科学研究科, 講師 (10302423)
YOH Keigyo University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor of Medicine, 大学院・人間総合科学研究科, 講師 (90323302)
SHIMIZU Yoshio University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor of Medicine, 大学院・人間総合科学研究科, 講師 (50359577)
山縣 邦弘 筑波大学, 大学院・人間総合科学研究科, 助教授 (90312850)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | IgA neohropathy / Staphylococcus Aureus / antignen / IgA1 / IgA2 / adhesin / S.aureus / high responder / low avidity antibody |
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| Research Abstract |
BACKGROUND : IgA nephropathy is the most common form of glomerulonephritis worldwide. We previously reported a novel form of glomerulonephritis with glomerular IgA deposits following methicillin-resistant Staphylococcus aureus (S.aureus) infection. We investigated the role of S.aureus related antigens in the immunopathogenesis of IgA nephropathy by producing several monoclonal antibodies against S.aureus surface antigens and determining the epitopes of deposited antigens in patients with IgA nephropathy. METHODS : Cell membrane proteins were isolated from cultured S.aureus. Mouse monoclonal antibodies against these proteins were generated, and their target epitopes were determined by antibody affinity chromatography and amino acid sequence analysis, and by monoclonal antibody screening of Escherichia coli clones transfected with plasmids from the Lambda S.aureus Genomic Library. Renal biopsy specimens from 116 patients with IgA nephropathy and 122 patients with other forms of renal disease were examined for glomerular antigen depositions by immunofluorescence microscopy. RESULTS : The major antigen recognized by monoclonal antibodies against S.aureus cell membrane was identified as the S.aureus cell envelope antigen designated ‘probable adhesin' (ACCESSION AP003131-77, Protein ID ; BAB41819.1). In 68.1% (79/116) of renal biopsy specimens from patients with IgA nephropathy, S.aureus cell envelope antigen was localized in the glomeruli, and the data confirmed that S.aureus cell envelope antigen was co-localized with IgA antibody in the glomeruli. No deposition of this antigen was detected in the glomeruli of patients with non-immune complex deposit forms of glomerulonephritis. CONCLUSION : S.aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.
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