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Study on the pathogenesis of Wegener's granulomatosis

Research Project

Project/Area Number 06671700
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Otorhinolaryngology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

INUYAMA Yukio (1995)  Hokkaido University School of Medicine Professor, 医学部, 教授 (70051480)

間口 四郎 (1994)  北海道大学, 医学部・附属病院, 助手 (20199665)

Co-Investigator(Kenkyū-buntansha) 犬山 征夫  北海道大学, 医学部, 教授 (70051480)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsWegener's granulomatosis / ANCA / cytokine / adhesion molecule / ウエゲナー
Research Abstract

This study examined the role of adhesion molecules in the pathogenesis of Wegener's granulomatosis (WG). For the cytokine, the titers of tumor necrosis factor-alpha (TNF-alpha) are not so high even in the active stage of the disease. The value of soluble ICAM-1 (inter-cellular adhesion molecule-1) in the active stage are significantly high compared with those in the inactive stage of the disease or in healthy volunteers. When we examined the sera of patients individually, the level of soluble ICAM-1 decreases gradually as the disease recover, and the correlation of them was apparently demonstrated. This result means that adhesion of the neutrophils with LFA-1 on its surface take place with the vascular endothelial cells in this disease. However, SLeX or LFA-1, the ligand of the neutrophil, was not revealed to become apparent when activated with TNF-alpha or cANCA (cytoplasmic-antineutrophil cytoplasmic antibody) lgG.It is supposed that integrin such as LFA-1 has two forms, resting form and active form, and its conformational change alter the affinity for the ligand. Further study is needed for this problem.
The study also examined the association between various human leukocyte antigens (HLA) and cANCA-positive WG in Japanese subjects to determine whether HLA antigens are involved in the pathogenesis of this disease. The study involved 16 subjects with cANCA-positive WG treated in our department. HLA-typing of the lymphocytes was performed using a lymphocyte microcytotoxicity assay. Of the subjects with cANCA-positive WG,62.5% (10/16) were positive for HLA-DR9, compared with 26% of the healthy control subjects. This HLA-DR9 elevation was statistically significant (P<0.01, Pc<0.05) ; we also noted a weaker association between HLA-B55 and cANCA-positive WG (P<0.05). The results indicated that an association may exist between certain HLA-class allotypes and WG.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 犬山征夫: "Wegener肉芽腫症の治療とネフロスカラー・C-ANCによる抗好中球細胞質抗体価の変動" 目耳鼻. 98. 974-983 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 犬山征夫: "Wegener肉芽腫症の診断と治療-耳鼻咽喉科の立場から-" 耳鼻頭頸. 67. 932-940 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakamaru Y: "Association of c-ANCA positive Wegener's granulomatosis with HLA antigens in Japanese patients" Rhinology in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shiroh Maguchi, Yukio Inuyama et al.: "Antineutrophil cytoplasmic antibody (c-ANCA) levels in relation to the treatment of Wegener's granulomatosis." Jounal of Otolaryngology of Japan. vol.98. 974-983 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shiroh Maguchi, Yukio Inuyama et al.: "Diagnosis and treatment of Wegener's granulomatosis" Jibi inkoka Tokeibu Geka. vol.67. 932-940 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakamaru Y,Maguchi S et al.: "Association of c-ANCA positive Wegener's granulomatosis with HLA antigens in Japanese patients" Rhinology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 間口四郎、滝沢昌彦他: "Wegener肉芽腫症の治療とネフロスカラー・C-ANCによる抗好中球細胞質抗体価の変動" 日耳鼻. 98. 974-983 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 間口四郎、滝沢昌彦他: "Wegener肉芽腫症の診断と治療-耳鼻咽喉科の立場から-" 耳鼻頭頸. 67. 932-940 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamaru Y,Maguchi Set al: "Association of c-ANCA positive Wegener's granulomatosis with HLA antigens in Japanese patients" Rhinology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 中丸裕爾: "Wegener肉芽腫症におけるHLAの関与について" 耳喉頭頸. 66. 698-701 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 滝沢昌彦: "Wegener肉芽腫症診断におけるC-ANCA ELISAキットの有用性" 耳喉頭頸. (in press).

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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