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Basic studies for the diagnosis of bullous diseases having pathologic changes at the basement membrane zone

Research Project

Project/Area Number 02044130
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKeio Gijuku University

Principal Investigator

NISHIKAWA Takeji  Keio University School of Medicine, Professor of Dermatology, 医学部・皮膚科, 教授 (50051579)

Co-Investigator(Kenkyū-buntansha) AMAGAI Masayuki  National Institute of Health, National Cancer Institute, Dermatology Branch, Res, 皮膚科, リサーチ:フェロー (90212563)
STANLEY John R.  National Institute of Health, National Cancer Institute, Dermatology Branch, Sen, 皮膚科, 上級研究員
EADY Robin A. J.  University of London, Institute of Dermatology, Professor of Cell Pathology, & S, 国立皮膚病研究所・細胞病理部, 主任教授
SHIMIZU Hiroshi  Keio University School of Medicine, Instructor of Dermatology, 医学部・皮膚科, 助手 (00146672)
HASHIMOTO Takashi  Keio University School of Medicine, Assistant Professor of Dermatology, 医学部・皮膚科, 講師 (20129597)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1991: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordshereditary and familial bullous diseases / autoimmune bullous diseases / bullous pemphigoid / immunoelectron microscopy / immunoblotting / immunoprecipitation / 抗表皮基底膜部抗体 / 線状IgA皮膚症
Research Abstract

There are a number of skin diseases in which epidermal basement membrane zone (BMZ) is affected. Therefore, the research for epidermal BMZ is important for both diagnostic and therapeutic respects. First, we investigated a series of antibodies against various components of BMZ, including LH7.2 and GB3 monoclonal antibodies and human monoclonal antibody against 23OkD bullous pemphigoid (BP) antigen. One approach is the precise localization of the antigens for these antibodies. For this purpose we have established cryofixation and cryosubstitution for immunoelectron microscopy in collaboration with Professor Eady, England.
Another approach is the determination of such antigens by using biochemical and molecular biological techniques. We discussed for these projects with Drs. Stanley and Amagai, U. S. A. and with Dr. Black, England, who also provided us with sera from their BP cases. Using immunoblot and immunoprecipitation method, we first showed that autoantigen profile is almost the same among Japanese, British and U. S. cases. We also found that although 230kD BP antigen is restricted to BMZ, 170kD BP antigen may exist in both BMZ and cell membrane of basal keratinocytes. Furthermore, although 170kD BP antigen was thought not to be detectable by immunoprecipitation, we showed 170kD BP antigen can be detectable by our improved immunoprecipitation method. In addition, we also established ELISA method using recombinant antigen protein produced by CDNA clone for 230kD BP antigen. This method can substitute the conventional immunofluorescence technique to detect anti-BMZ antibodies in BP sera.
Another important disease is linear IgA bullous dermatosis (LAD). We have investigated for LAD autoantigen as collaboration work with Professor Zone, U. S. A. and Drs. Black and Wojnarowska, England. We confirmed that some LAD sera specifically react with 97kD protein. However, the real nature of this 97kD protein should be clarified by further confirmative studies.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] 橋本 隆: "免疫ブロット法による自己免疫性水疱症の診断" 臨床皮膚科. 45. 115-120 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka M.,Hashimoto T.,Amagai M.,Shimizu N.,Ikeguchi N.,Tsubata T.,Hasegawa A.,Miki K.,Nishikawa T.: "Characterization of bullous pemphigoid antibodies by use of recombinant bullous pemphigoid antigen proteins." Journal of Investigative Dermatology. 97. 725-728 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ebihara T.,Hashimoto T.,Kudoh J.,Gamou S.,Shimizu N.,Nishikawa T.: "Detection of the 170kD bullous pemphigoid antigen by immunoprecipitation"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto T.,Ebihara T.,Bhogl B.S.,Black M.M.,Stanley J.R.,Nishikawa T.: "Comparative study of bullous pemphigoid antigens among Japanese,British and U.S.patients indicates similar antigen profiles."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto T.,Ebihara T.,Gamou S.,Shimizu N.,Nishikawa T.: "Human hybridomas constructed with EpsteinーBarr virus transformed cell lines producing human monoclonal antiーbasement membrane zone antibodies."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shimizu H.,IshidaーYamamoto A.,Eady R.A.J.: "The use of silverーenhanced 2ーnm gold probe for light and electron microscopic localization of intraー and extracellular antigens in skin." Journal of histochemistry and Cytochemistry.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 清水 宏: "皮膚免疫電顕の応用と展望" 皮膚病診療. 12. 1079-1086 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 清水 宏: "皮膚免疫電顕の基礎と臨床ーペルオキシダ-ゼ法から金コロイド法へ" 臨床皮膚科. 44. 1041-1051 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 杉 俊之,橋本 隆: "類天疱瘡ーヒト抗表皮基底膜部単クロ-ン抗体による解析" 臨床皮膚科. 44. 499-503 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 橋本 隆: "水疱性疾患の新しい知見について免疫ブロット法による天疱瘡抗原の解析とその臨床的応用" 皮膚科の臨床. 32. 783-789 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shimizu,H.,McDonald J.N.,Gunner D.B.,Black M.M.,Bhogal B.,Leigh I.M.,Whitehead P.C.,Eady R.A.J.: "Epidermolysis bullosa acquisita antigen and Cーterminal of type VII collagen have common immunoーlocalization on anchoring fibrils and lamina densa of basement membrane." British Journal of Dermatology. 122. 577-585 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka T.,Korman N.J.,Shimizu H.,Eady R.A.J.,KlausーKovtun V.,Cehrs K.,Stanley J.R.: "Productionof rabbit antibodies against carboxyーterminal epitopes encoded by bullous pemphigoid cDNA." Journal of Investigative Dermatology. 94. 617-623 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Amagai M.,Hashimoto T.,Tajima S.,Inokuchi Y.,Shimizu N.,Saito M.,Miki K.,Nishikawa.T.: "Partinal cDNA cloning of the 230ーkD mouse bullous pemphigoid antigen by use of a human monoclonal antiーbasement membrane zone antibody." Journal of Investigative Dermatology. 95. 252-259 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shimizu H.,Hashimoto T.,Nishikawa T.,Eady R.A.J.: "Human monoclonal antiーbasement membrane zone antibodies deriyed from virally transformed lymphocytes of a patient with bullous pemphigoid recognize epitopes associated with hemidesmosomes." British Journal of Dermatology. 124. 217-220 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 清水 宏,O.M.V.Schofield,R.A.J.Eady: "胎児皮膚生検による先天性表皮水疱症の出生前診断(Prenatal diagnosis)" 日本皮膚科学会雑誌. 101. 539-545 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka M, Hashimoto T, Amagai M, Shimizu N, Ikeguchi N, Tsubata T, Hasegawa A, Miki K, and Nishikawa T.: "Characterization of bullous pemphigoid antibodies by use of recombinant bullous pemphigoid antigen proteins" Journal of Investigative Dermatology. 97. 725-728 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ebihara T, Hashimoto T, Kudoh J, Gamou S, Shimizu N, and Nishikawa T.: "Detection of the 170kD bullous pemphigoid antigen by immunoprecipitation"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto T, Ebihara T, Bhogal BS, Black MM, Stanley JR, and Nishikawa T.: "Comparative study of bullous pemphigoid antigens among Japaness, British and U. S. patients indicates similar antigen profiles."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto T, Ebihara T, Gamou S, Shimizu N, and Nishikawa T.: "Human hybridomas constructed with Epstein-Barr virus transformed cell lines producing human monoclonal anti-basement membrane zone antibodies."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shimizu H, Ishida-Yamamoto A, and Eady RAJ.: "The use of silver-enhanced 2-nm gold probe for light and electron microscopic localization of intra- and extracellular antigens in skin." Journal of Histochemistry and Cytochemistry.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 清水 宏,O.M.V.Schofield,R.A.J.Eady: "胎児皮膚生検による先天性表皮水疱症の出生前診断(Prenatal diagnosis" 日本及皮膚学会雑誌. 101. 539-545 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 橋本 隆: "免疫ブロット法による自己免疫小疱症の診断" 臨床皮膚科. 45. 115-120 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 清水 宏: "皮膚免疫電顕の応用と展望" 皮膚病診療. 12. 1079-1086 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 清水 宏: "皮膚免疫電顕の基礎と臨床ーペルオキシダ-ゼ法から金コロイド法へ" 臨床皮膚科. 44. 1041-1051 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 杉 俊之 橋本 隆: "類天疱瘡ーヒト抗表皮基底膜部単クロ-ン抗体による解析" 臨床皮膚科. 44. 499-503 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 橋本 隆: "水疱性疾患の新しい知見について:免疫ブロット法による天疱瘡抗原の解析とその臨床的応用" 皮膚科の臨床. 32. 783-789 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shimizu H,.McDonald J N,Gunner D B,Black M M,Bhogal B,Leigh I M,Whitehead P C,Eady R A J.: "Epidermolysis bulosa acquisiten and Cーterminal of type VII collagen have common immunoーlocalization on anchoring fibrils and lamina densa of basement membrane." British Joural of Dermatology. 122. 577-585 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tanaka T,Korman N J,Shimizu H,Eady R A J,KlausーKovtun V,Cehrs K,Stanley J R.: "Production of rabbit antibodies against carboxyーterminal epitopes encoded by bullous pemphigid cDNA." Journal of Investigative Dermatology. 94. 617-623 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Amagai M,Hashimoto T,Tajima S,Inokuchi Y,Shimizu N,Satio M,Miki K,Nishikawa T.: "Partial cDNA cloning of the 230ーkD mouse bullous pemphigoid sntigen by use of a human monoclonal antiーbasement membrane antibody." Journal of Investigative Dermatology. 95. 252-259 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shimizu H,Hashimoto T,Nishikawa t,Eady R A J.: "Human monoclonal antiーbasement membrane zone antibodies derived from virally transformed lymphocytes of a pstient with bullous pemphigoid recognize epitopes associated with hemidesmosomes." British Journal of Dermatology.

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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