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Investigations of pathogenesis and therapeutic approach for IgA nephropathy.-A trial of experimental mouse model of glomerular deposition of human IgA-

Research Project

Project/Area Number 16590804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionFujita Health University

Principal Investigator

HIKI Yoshiyuki  Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (20156566)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Satoshi  Fujita Health University, School of Medicine, Professor, 医学部, 教授 (50340229)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsIgA1 hinge / O-glycans / IgA nephropathy / KM mouse / galactose / sialic acid / IgA1ヒンジ / O結合型糖鎖 / IgA1 / N-アセチルガラクトサミン / メサンギウム / 0結合型糖鎖
Research Abstract

The KM mouse lacks endogenous genes for immunoglobulins and carries the human entire human IgH locus and the IgLk transgene. Therefore, human IgA1 does not provoke a hetero-immune response. We had observed mesangial IgA deposits in KM mice given desialo-degalacto (DeS/DeGal) IgA1. In this study, the mice were immunized with synthetic IgA1 hinge (glyco-)peptide before administration of DeS/DeGal IgA1, and the effects of the pre-immunization were evaluated. Mice were divided into sHP, 5Ga1NAc-sHP and non-immunization groups. In two pre-immunization groups, KLH-conjugated sHP or KLH-5GalNAc-sHP, which has five GalNAc residues, was subcutaneously given three times every two weeks. Two weeks after the final pre-immunization, DeS/DeGal IgA1 was daily administered for five weeks. Serial serum levels of anti-sHP and anti-IgA1antibodies were evaluated by ELISA. On the day of the last administration of IgA1, renal biopsy was performed. Mesangial IgA deposits were observed in all non-immunized mice. In pre-immunized mice, IgA deposition was not detected in six of 13 sHP mice and one of four 5GalNAc-sHP mice. The intensities of IgA deposits were significantly different between sHP groups and non-immunized (p=0.003) groups. There was a significant inverse correlation between the intensities of IgA deposits and the anti-sHP antibody titers (p=0.016). These results suggest that the anti-IgA1 hinge peptide antibody plays a role in the inhibition of glomerular IgA deposition.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 2005 2004 Other

All Journal Article (16 results) Book (1 results)

  • [Journal Article] IgA 腎症のステロイド療法2007

    • Author(s)
      小林豊, 比企能之
    • Journal Title

      IgA 腎症の基礎と臨床 IgA 腎症研究会第30回記念

      Pages: 71-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] IgA 腎症とIgA分子構造 -糖鎖構造を中心にして-2007

    • Author(s)
      比企能之
    • Journal Title

      IgA 腎症の基礎と臨床 IgA 腎症研究会第30回記念

      Pages: 44-53

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Steroid therapy for IgA nephropathy2007

    • Author(s)
      Kobayashi Y., Hiki Y
    • Journal Title

      Fundamental and clinical investigations for IgA nephropathy

      Pages: 71-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IgA nephropathy and structure of IgA molecules -From the aspect of carbohydrate side chains-2007

    • Author(s)
      Hiki Y
    • Journal Title

      Fundamental and clinical investigations for IgA nephropathy

      Pages: 44-53

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structural analyses of O-glycan sugar chains on IgAl hinge region using SELDI-TOFMS with various lectins.2006

    • Author(s)
      Takahashi T., Hiki Y., et al.
    • Journal Title

      Biochem. Biophs. Res. Commun 350

      Pages: 580-587

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structural analyses of O-glycan sugar chains on IgA1 hinge region using SELDI-TOFMS with various lectins.2006

    • Author(s)
      Takahashi T., Hiki Y., et al.
    • Journal Title

      Biochem.Biophs.Res.Commu 350

      Pages: 480-587

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structural analyses of O-glycan sugar chains on IgA1 hinge region using SELDI-TOFMS with various lectins.2006

    • Author(s)
      Takahashi T., Hiki Y., et al.
    • Journal Title

      Biochem. Biophs. Res. Commun 350

      Pages: 580-587

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Continuous administration of human desialo-degalacto IgA1 causes mesangial IgA deposition in KM mouse having entire human Ig Loci.2005

    • Author(s)
      Hiki Y, Takahashi K, Itoh M et al.
    • Journal Title

      Nephrology 10(6)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Detemination of aberrant O-glycosylation in the IgA1 hinge region by electron capture dissociation fourier transform ion cycloton resonance mass spectrometry.2005

    • Author(s)
      Renfrow MB, Cooper HJ, Hiki Y, et al.
    • Journal Title

      J Biol Chem 280

      Pages: 19136-19145

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IgA腎症における糸球体硬化2005

    • Author(s)
      高橋和男, 比企能之
    • Journal Title

      腎と透析 62

      Pages: 53-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IgA腎症とIgA1ヒンジ部ムチン型糖鎖不全2005

    • Author(s)
      比企能之
    • Journal Title

      腎と透析 58

      Pages: 331-338

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Detection of gender difference and epitope specificity of IgG antibody activity against IgA1 hinge portion in IgA nephropathy patients by using synthetic hinge peptide and2004

    • Author(s)
      Nakamura, I., Iwase, H., Arai K., Nagai Y, Toma K., Katsumata, T., Hiki Y.
    • Journal Title

      Nephrology 9

      Pages: 26-30

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Application of Mass Spectrometry to IgA Nephropathy : Structure and Biological Analyses of Underglycosylated IgA1 Molecules.2004

    • Author(s)
      Yasuda, Y., Horie, A., Odani, H., Iwase, H., Hiki Y.
    • Journal Title

      Contrib. Nephrol 141

      Pages: 170-188

    • Related Report
      2004 Annual Research Report
  • [Journal Article] IgA nephropathy and tonsils. -An approach from the structure of IgA1 produced by tonsillar lymphocytes.2004

    • Author(s)
      Hiki Y, Horie A, Yasuda Y, Iwase H, Sugiyama S
    • Journal Title

      Acta Otolaryngol Supple55

      Pages: 28-31

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Determination of aberrant O-glycosylation in the IgA1 hinge region by electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry.

    • Author(s)
      Renfrow MB, Cooper HJ, Tomana M, Kulhavy R, Hiki Y, Toma K, Mestecky J
    • Journal Title

      J Biol Chem (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] IgA腎症とIgA1ヒンジ部ムチン型糖鎖不全

    • Author(s)
      比企能之, 岩瀬仁勇, 杉山 敏
    • Journal Title

      腎と透析 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Book] 最新医学別冊 新しい診断と治療のABC(23) IgA腎症2004

    • Author(s)
      比企能之(富野康日己編集)
    • Total Pages
      200
    • Publisher
      最新医学社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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