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Development of disease activity monitoring assay system by ELISA using recombinant pemphigus antigens

Research Project

Project/Area Number 09670895
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

AMAGAI Masayuki  Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (90212563)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Takeji  Keio University, School of Medicine, Professor, 医学部, 教授 (50051579)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsAutoimmune disease / Pemphigus / ELISA / Diagnostic tool / Disease activity / Cadherin / Dersmoglein / Cell adhesion
Research Abstract

Pemphigus is an autoimmune blistering disease and has two major subtypes, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating anti-Dsg1 and/or anti-Dsg3 IgG autoantibodies. We have previously developed ELISAs using recombinant Dsg1 and Dsg3 expressed by baculovirus as a diagnostic tool for pemphigus. The purpose of this study was to evaluate the practical application of these ELISAs for clinical use with a large number of serum samples. We used 81 PV sera, 48 PF sera, 114 bullous pemphigoid (BP) sera, 124 collagen disease sera, 8 sera of other non-pemphigus bullous diseases and 179 normal control sera. A cutoff value was determined by Receiver-Operating-Characteristic (ROC) plots. 47 of 48 PF sera (97.9%) were positive in the Dsg1 ELISA and 79 of 81 PV sera (97.5%) were positive in the Dsg3 ELISA, while only 2(1.1%) and 4(2.2%) of 179 normal sera were positive in Dsg1 and Dsg3 ELISAs, respectively. However, some disease control sera of BP arid collagen diseases exceeded the cutoff value. Introduction of a gray zone helped to decrease the number of those false positive sera. Furthermore, in 11 patients studied, the respective Dsg1 and Dsg3 ELISA scores showed parallel fluctuation with the disease activity along the time course. We proposed a diagnostic criteria for pemphigus based on ELISA reactivity ; if a serum is positive against Dsg3 it indicates diagnosis of PV, regardless of reactivity against Dsg1 ; if a serum is negative for Dsg3 and positive for Dsg1, it indicates diagnosis of PF.We concluded that these Dsg1 and Dsg3 ELISAs provide a simple, sensitive and highly specific assay for the diagnosis of patients with PV and PF and that these ELISAs may be a valuable tool to monitor the disease activity.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Ishii K, Amagai M, Hall RP, Hashimoto T, Takayanagi A, Gamou S, Shimizu N, Nishikawa T: "Characterization of autoantibodies in pemphigus using antigen-specific ELISAs with baculovirus expressed recombinant desmogleins" J Imunol. 159. 2010-2017 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amagai M, Nishikawa T, Nousari HC, Anhalt GJ, 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(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amagi M, Tsunoda K, Zillikens D, Nagai T, Nishikawa T: "The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile" J Am Acad Dermatol. 40. 167-〓70 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lenz P, Amagai M, Volc-Platzer B, Stingl G, Kimbauer R: "Desmoglein3-ELISA : A pemphigus vulgaris-specific diagnostic tool" Arch Dermatol. 135. 143-148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amagai M, Komai A, Hashimoto I, Shirakata Y, Hashimoto K, Yamada T, Kitajima Y, Ohya K, Iwanami H, 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(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishii K, Amagai M, Komai A, Ebihara T, Chorzelski TP, Jablonska S, Ohya K, Nishikawa T, Hashimoto T: "Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus" Arch Dermatol. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishii K,Amagai M,Hall RP,Hashimoto T,Takayanagi A,Gamou S,Shimizu N,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
      1998 Final Research Report Summary
  • [Publications] Amagai M,Nishikawa T,Nousari HC,Anhalt GJ,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
      1998 Final Research Report Summary
  • [Publications] Amagai M,Tsunoda K,Zillikens D,Nagai T,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
      1998 Final Research Report Summary
  • [Publications] Lenz P,Amagai M,Volc-Platzer B,Stingl G,Kirnbauer R: "Desmoglein3 - ELISA : A pemphigus vulgaris-specific diagnostic tool." Arch Dermatol. 135. 143-148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amagai M,Komai A,Hashimoto T,Shirakata Y,Hashimoto K,Yamada T,Kitajima Y,Ohya K,Iwanami H,Nishikawa T: "Usefulness of enzyme-linked immunosorbent assay (ELISA) using recombinant desmogleins 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
      1998 Final Research Report Summary
  • [Publications] Ishii K,Amagai M,Komai A,Ebihara T,Chorzelski TP,Jablonska S,Ohya K,Nishikawa T,Hashimoto T: "Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus." Arch Dermatol. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amagai M,Nishikawa T,Nousari HC,Anhalt GJ,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)

    • Related Report
      1998 Annual Research Report
  • [Publications] Amagai M,Tsunoda K,Zillikens D,Nagai T,Nishikawa T: "The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile" J Am Acad Dermatol. 40. 167-170 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Proby C,Fujii Y,Owaribe K,Nishikawa T,Amagai M: "Human autoantibodies against HD1/plectin in paraneoplastic pemphigus" J Invest Dermatol. 112. 153-156 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lenz P,Amagai M,Volc-Platzer B,Stingl G,Kirnbauer R: "Desmoglein3-ELISA:A pemphigus vulgaris-specific diagnostic tool" Arch Dermatol. 135. 143-148 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Amagai M,Komai A,Hashimoto T,Shirakata Y,Hashimoto K,Yamada T,Kitajima Y,Ohya K,Iwanami H,Nishikawa T: "Usefulness of enzyme-linked immunosorbent assay(ELISA)using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus" Br J Dermatol. 140. 351-357 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishii K,Amagai M,Komai A,Ebihara T,Chorzelski TP,Jablonska S,Ohya K,Nishikawa T,Hashimoto T: "Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus" Arch Dermatol. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hernandez C.et al: "Pemphigus foliaceus:preferential binding of IgG1 and C3 at the upper epidermis." Br J Dermatol. 136. 249-252 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubo A.et al.: "Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen(desmoglein 3)" Br J Dermatol. 137. 109-113 (1997)

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

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashimoto T.et al.: "Human deswocallin 1(Dsc1)is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus." J Invest Dermatol. 109. 127-131 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shirakata Y.et al.: "Lack of mucosal involument inpewphigus foliaceus may be due to low expression of desmoglein 1." J Invest Dermatol. 110. 76-78 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] HerTl M.et al.: "Recognition of desmoglein 3 by autoreactive T cells in pemphigas vulgaris patients and normals." J Invest Dermatol. 110. 62-66 (1998)

    • Related Report
      1997 Annual Research Report

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

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