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Research of disease selective immunotherapy in autoimmune diseases

Research Project

Project/Area Number 09556068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Applied veterinary science
Research InstitutionTokyo University of Agriculture & Technology (1999)
Gifu University (1997-1998)

Principal Investigator

IWASAKI Toshiroh  Tokyo University of Agriculture & Technology, Department of Veterinary Internal Medicine, Professor, 農学部, 教授 (50262754)

Co-Investigator(Kenkyū-buntansha) AMAGAI Masayuki  Keio University School of Medicine, Department of Dermatology, Lecturer, 医学部, 講師 (90212563)
堀内 正  第一製薬, 創薬基盤研究所, 所長(研究職)
志水 泰武  岐阜大学, 農学部, 助教授 (40243802)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsdog / pemphigus / ELISPOT / desmoglein / autoimmune disease / animal model / desmonsome / 自己免疫疾患 / 天疱痘 / デスモソーム
Research Abstract

Pemphigus is a life-threatening autoimmune blistering disease of the skin and mucous membranes. In patients with pemphigus, circulating autoantibodies against cell surface of keratinocytes in stratified squamous epithelia play a pathogenic part, and cause loss of cell-cell adhesion with resultant blister formation. Since the detection of autoantibodies by indirect immunofluorescence in canine pemphigus is usually difficult probably due to the low sensitivity of the substrate, several substrates for immunofluorescence were studied. As a result, bovine esophagus showed highest sensitivity and specifity. For investigating the autoantigens directed by the serum of pemphigus foliaceus, cloning and sequencing of canine desmoglein 1 (Dsg1) were performed using cDNA library from canine skin. Fusion proteins of Dsg1 expressed in baculovirus were made. These proteins reacted with sera from human patients with pemphigus foliaceus, suggesting that canine Dsg1 crossreacted with human autoantibodies from pemphigus foliaceus. ELISPOT (enzyme-linked immunospot assay) was developed for the detection of antigen-specific B cells in patients with pemphigus. This method will provide us to analyze frequencies of Dsg-specific IgG producing and memory B cells.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Nishifuji K et al.: "Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay"J Invest Dermatol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii K et al.: "Desmoglein 1 and desmoglein 3 are the target autoantibodies in herpetiformis pemphifgus"Arch dermatol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M et al.: "Usefulness of enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3 for serodiagnosis of pemphigus"Br J. Dermatol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M et al.: "Antibodies against desmoglein 3(pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus"J Clin Invest.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwasaki T et al.: "Detection of canine pemphigus foliaceus autoantigen by immunoblotting"Vet Immunol Immunopathol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M: "The clinical phenotype of pemphigus is defined by the antidesmoglein autoantibody profile"J Am Acad Dermatol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii K, Amagai M, Hall RP, Hashimoto T, Takayanagi A, Gamou S, Shimizu N and Nishikawa T: "Characterization of autoantibodies in pemphigus using antigen-specific ELISAs with baculovirus expressed recombinant desmogleins"J. Immunol.. 159. 2010-2017 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hashimoto T, Kiyokawa C, Mori O, Miyasato M, Chidgey MAJ, Garrod DR, Kabayshi Y, Komiri K, Ishii K, Amagai, and Nishikawa T: "Human desmocollin 1 (Dsc 1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pumphigus"J Invest Dermatol. 109. 127-131 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwasaki T, Shimizu M, Obata H, Isaji M, Yanai T, Kitagawa H and Sasaki Y: "Detection of canine pemphigus folianceus autoantigen by immunoblotting"Vet Immunol Immounopathol. 59. 1-10 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shirakawa Y, Amagai M, M. Hanakawa Y, Nishikawa T and Hashimoto K: "Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1"J Invest Dermatol. 110. 76-78 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Heartl M. Amagai M, Sundaram H, Stanley JR, Ishii K and Katz SI: "Recognition of dosmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals"J Invest Dermatol. 110. 62-66 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Heartl M. Karr RW, Amagai M and Katz SI: "Heterogenous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals"J Invest Dermatol. 110. 388-392 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M, Nishikawa T, Nousari HC, Anhalt GJ and Hashimoto T: "Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice"J Clin Invest. 102. 775-782 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Proby C, Fujii Y, Owaribe K, Nishikawa T and Amagai M: "Human autoantibodies against HD1/plectin in paraneoplastic pemphigus"J Invest Dermatol. 112. 153-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M, Komai A, Hashimoto T, Shirakawa Y, Hashimoto K, Yamada T, Kitajima y, Ohya K, Iwanami H and Nishikawa T: "Usefulness of enzyme-linked immunosorbent assay (ELISA) using recombinant desmoglein 1 and 3 for serodiagnosis of pemphigus"Br J Dermatol. 140. 351-357 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Amagai M, Tsunoda K, Zillikens D, Nagai T and Nishikawa T: "The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile"J Am Acad Dermatol. 40. 167-170 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii K, Amagai M, Komai A, Ebihara T, Chorzelski TP, Jablonska S, Ohya K, Nishikawa T and Hashimoto T: "Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus"Arch Dermatol. 135. 943-947 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishifuji K, Amagai M, Kuwana M, Iwasaki T and Nishikawa T: "Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot (ELISPOT) assay : requirement of T cell collaboration for antibody production"J Invest Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishifuji K et al.: "Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay"J Invest Dermatol. 114・1. 88-94 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishii K et al.: "Desmoglein 1 and desmoglein 3 are the target autoantibodies in herpetiformis pemphigus"Arch Dermatol. 135. 943-947 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Amagai M et al.: "Usefulness of enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3 for serodiagnosis of pemphigus"Br J Dermatol. 140. 351-357 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Amagai M et al.: "Antibodies against desmoglein 3 (Pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus"J Clin Invest. 102・4. 775-782 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] lwasaki T et al.: "Detection of canine pemphigus foliaceus autoantigen by immunoblotting"Vet Immunol Immunopathol. 59・1. 1-10 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Amagai M: "The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile"J Am Acad Dermatol. 40・2. 167-169 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwasaki.T.et al.: "Detection of canine pemphigus foliaceus autoautigen by immunoblotting" Vet.Immunol Immunopathol. 59. 1-10 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] IWASAKI.T.et al.: "The expression of vasement membrane zone and integrin receptors in canine keratinocytes during wound healing" Adv.Vet.Dermatol. 3. 339-354 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hernandez C.et al.: "Pemphigus foliaceus : preferential binding of IgGI and C3 at the upper epidermis" Br J Dermatol. 136. 249-252 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubo A.et al.: "Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmol glein3)" Br J Dermatol. 137. 109-113 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishii K et al.: "Characterization of autoantibodies in pemphigus using antigen-specific ELISAs with baculovirus expressed recombinant desmogleins" J Immunol. 159. 2010-2017 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.NAGATA et al.: "Non-lethal junctional epidermolysis bullosa in a dog" British Journal of Dermatology. 137. 445-449 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] IWASAKI T.et al.: "Detection of canine pemphigus foliaceus autoautigen by immunoblotting" Vet.Immunol Immunopathol. 59. 1-10 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] IWASAKI T.et al.: "The expression of basement membrane zone and integrin recepters in canine keratinocytes during wound healing" Adv.Vct.Dermatol.3(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hernandez C et al.: "Pemphigus foliaceus preferential binding of IgG1 and C3 at the upper epidernis" Br J Dermatol 136. 136. 249-252 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubo A.et al.: "Herpetiform penphigug showing reactivity with pemphigus rulgaris antigen (desmolglein 3)" Br J Dermatol. 137. 169-113 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishii K et al.: "Characterization of autoantibodies in pemphigus using antigen specific ELTSAs with baculourus express" J Immunol. 159. 2010-2017 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashimoto T.et al.: "Human desinocollin 1(Dsg 1)is an antoantigen for the subcorneal pustual dermatosis type of IgA pemphigs" J Invest Dermatol. 109. 127-131 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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