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2006 Fiscal Year Final Research Report Summary

THE MECHANISM OF NEPHRITOGENIC ANTI-DNA ANTIBODY PRODUCTION IN LUPUS NEPHRITIS

Research Project

Project/Area Number 17591026
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionTohoku University

Principal Investigator

HIRABAYASHI Yasuhiko  Tohoku University, Tohoku University Hospital, Lecturer (70312577)

Co-Investigator(Kenkyū-buntansha) ISHII Tomonori  Tohoku University Hospital, 病院, Research Associate (10282138)
TAKASAWA Naruhiko  Graduate School Of Medicine, 大学院・医学系研究科, Research Associate (50359519)
Project Period (FY) 2005 – 2006
KeywordsSystemic Lupus Nephritis / Lupus Nephritis / Anti-DNA antibody
Research Abstract

The aim of the present study is to elucidate the antigenic trigger for the production of human nephritogenic anti-DNA antibodies. We found that a human monoclonal nephritogenic O-81 anti-DNA antibody bound to an endoplasmic reticulum stress-inducible protein, Herp.
1. The anti-DNA or anti-Herp antibodies were obtained from the patients with active lupus nephritis by using a DNA-immobilized or a Herp-immobilized agarose, respectively. Lupus anti-DNA antibodies bound to Herp. Moreover, the anti-Herp antibodies showed specific binding to DNA.
2. Each 6-week-old BALB/c female mouse was immunized intraperitoneally with Herp or Hen Egg Lysozyme (HEL). immunization with Herp, but not HEL, elicited anti-dsDNA as well as anti-ssDNA antibodies in BALB/c mice and formed the deposits of IgG in the renal glomeruli.
3. The PBLs from SLE patients or healthy subjects were stained with a monoclonal anti-Herp antibody. Herp was spontaneously expressed in the PBLs of patients with active SLE, but in the PBLs of healthy subjects. The expression of Herp in the SLE PBLs was observed during the 72 hours in vitro culture without any stimulation. No expression of Herp was observed in healthy PBLs.
4. To assess the antigenicity of Herp, the PBLs were cultured with Herp for 6 days, and the number of anti-DNA antibody producing clones was measured by ELISPOT assay. The number of anti-DNA antibody producing clones in the PBLs from active SLE patients increased in vitro after stimulation with Herp, but not with HEL or dsDNA. The PBLs form inactive SLE patients or healthy subjects did not respond to the stimulation with Herp.
These results imply that an inducible intracellular self protein could be a trigger for human nephritogenic anti-DNA autoantibodies, where ER stress may be noted.

  • Research Products

    (11 results)

All 2007 2006

All Journal Article (11 results)

  • [Journal Article] A potential trigger of nephritogenic anti-DNA antibodies inlupus nephritis2007

    • Author(s)
      Yasuhiko Hirabayashi
    • Journal Title

      Annals of the New York Academy of Sciences 1108

      Pages: 92-95

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gastrojejunostomy and Duodenojejunostomy for Megaduodenumin Systemic Sclerosis Sine Scleroderma2007

    • Author(s)
      Katsuyoshi Kudoh
    • Journal Title

      Digestive Diseases and Sciences 52

      Pages: 2257-2260

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A potential trigger of nephritogenic anti-DNA antibodies in lupus nephritis2007

    • Author(s)
      Yasuhiko Hirabayashi
    • Journal Title

      Annals of the New York Academy of Sciences 1108

      Pages: 92-5

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gastrojejunostomy and Duodenojejunostomy for Megaduodenum in Systemic Sclerosis Sine Scleroderma2007

    • Author(s)
      Katsuyoshi Kudoh
    • Journal Title

      Digestive Diseases and Sciences 52

      Pages: 2257-2260

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A potential trigger of nephritogenic anti-DNA antibodies in lupus nephritis2006

    • Author(s)
      Yasuhiko Hirabayashi
    • Journal Title

      Autoimmunity Reviews

      Pages: 87-88

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Q fever with clinical features resembling systemic lupuserythematosus2006

    • Author(s)
      Hiroshi Ohguchi
    • Journal Title

      Internal Medicine 45

      Pages: 323-326

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 自己抗体と細胞ストレス:抗DNA抗体産生における小胞体ストレス応答性蛋白の役割2006

    • Author(s)
      平林泰彦
    • Journal Title

      日本臨床免疫学会会誌 29

      Pages: 65-72

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 抗DNA抗体産生における小胞体蛋白の意義2006

    • Author(s)
      平林泰彦
    • Journal Title

      臨床免疫 45

      Pages: 650-655

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Q fever with clinical features resembling systemic lupus erythematosus2006

    • Author(s)
      Hiroshi Ohguchi
    • Journal Title

      Internal Medicine 45

      Pages: 323-326

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of cell stress in systemic autoimmune disease2006

    • Author(s)
      Yasuhiko Hirabayashi
    • Journal Title

      Nihon Rinsho Meneki Gakkai Kaishi 29

      Pages: 65-72

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of endoplasmic reticulum protein in anti-DNA antibody production2006

    • Author(s)
      Yasuhiko Hirabayashi
    • Journal Title

      Rinsho Meneki 45

      Pages: 650-655

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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