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Search for factors which affect the activation of complement ; relation to inflammation and susceptibility to infection

Research Project

Project/Area Number 16591048
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

TERAI Itaru  Health Sciences University of Hokkaido, Institute of Medical Science, Lecturer, 個体差医療科学センター, 講師 (40337043)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Kunihiko  Hokkaido University Graduate School, School of Medicine, Professor Emeritus, 大学院・医学研究科・酪農学園大学・酪農学部, 名誉教授・客員教授 (60091451)
MAFUNE Naoki  Rakunougakuen University, Faculty of Dairy Science, Department of Food Science, Professor, 酪農学部, 教授 (70241304)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsmannose-binding lectin / complement activation / lectin pathway / immunodeficiency / immunoglobulin A / IgA nephropathy
Research Abstract

MBL is reported to bind to agalactosyl IgG, but not to normally galactosylated (native) IgG. It was recently reported that serum polymeric IgA in its native form reacts with MBL, whereas a more recent report has claimed that native IgD and IgE, and possibly IgM, do not. This led us to investigate whether IgA is truly reactive with MBL. To accomplish this, we collected purified human Igs, of various classes, subclasses, and allotypes and tested their ability to bind to MBL using an ELISA method. Among these preparations, only one (monoclonal IgA2m(2) : Kur) exhibited significant MBL binding. In particular, polymeric or monomeric forms of our normal serum IgA preparation lacked any ability to bind to MBL whatsoever. However, all the Ig preparations which had not bound to MBL became able to do so when they were degalactosylated with a galactosidase treatment, and the binding was further enhanced by acidic denaturation of the Igs. Among the degalactosylated and/or acid-denatured IgA, the IgA2 subclass exhibited a higher level of MBL binding than did IgA1. Our results suggest that MBL does not bind to native Igs (viewed in principal as "self" components), and that only Igs with abnormal glycosylation (degalactosylated forms) and/or denaturation would be MBL-reactive. It has been reported that in IgA nephropathy, IgA2 deposition in glomeruli is associated with MBL and complement activation through the lectin pathway. This would imply that the deposited IgA2 would be in a degalactosylated form and able to bind to MBL, further supporting the influence of IgA glycosylation defects in the pathogenesis of this disease.

Report

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

    (6 results)

All 2006 2005

All Journal Article (6 results)

  • [Journal Article] Degalactosylated and/or denatured IgA, but not native IgA in any form, bind to mannose-binding lectin(MBL)2006

    • Author(s)
      Itaru Terai, Kunihiko Kobayashi, Jean-Pierre Vaerman, Naoki Mafune
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Degalactosylated and/or denatured IgA, but not native IgA in any form, bind to mannose-binding lectin (MBL)2006

    • Author(s)
      Itaru Terai, Kunihiko Kobayashi, Jean-Pierre Vaerman, Naoki Mafune
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Sero-Epidemiological Survey of Gelatin Sensitization in Young Japanese Children During the 1979-1996 Period2005

    • Author(s)
      Saito A., Kumagai H., Kojima H., Terai I., Yamanaka T., et al.
    • Journal Title

      Scand J Immunol 61

      Pages: 376-379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Sero-Epidemiological Survey of Gelatin Sensitization in Young Japanese Children During the 1979-1996 Period2005

    • Author(s)
      Saito A., Kumagai H., Kojima H., Terai I., Yamanaka T.et al.
    • Journal Title

      Scand J Immunol 61

      Pages: 376-379

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Sero-Epidemiological Survey of Gelatin Sensitization in Young Japanese Children During the 1979-1996 Period.2005

    • Author(s)
      Saito A., Kumagai H., Kojima H., Terai I..Yamanaka T.et al.
    • Journal Title

      Scand J Immunol 61

      Pages: 376-379

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A sero-epidemiological survey of gelatin sensitization in young Japanese children during a recent 18 year period.2005

    • Author(s)
      Saito A., Kumagai H., Kojima H., Terai I., Yamanaka T.et al.
    • Journal Title

      Scand J Immunol (in press)

    • Related Report
      2004 Annual Research Report

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

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