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Analysis of autoimmune bullous diseases using recombinant proteins of BP230 and BP180

Research Project

Project/Area Number 11670857
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKurume University School of Medicine

Principal Investigator

KOMAI Ayako  Dermatology, Kurume University School of Medicine. Lecturer, 医学部, 助手 (70281532)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Takashi  Dermatology Kurume University School of Medicine. Professor, 医学部, 教授 (20129597)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsAutoimmune disease / Bullous pemphigoid / hemidesmosome / Recombinant protein / Immunoblotting / ELISA / BP230 / BP180 / 自己免疫性天疱瘡 / 自己抗体 / 腫瘍随伴性天疱瘡
Research Abstract

We have obtained 3 cDNAs covering entire BP230 by PCR amplification using appropriate primers and cDNA library prepared from mRNA of cultured keratinocytes. We inserted these cDNAs into bacterial expression vector, pGEX, and produced recombinant fusion proteins to GST.Using immunoblotting of these recombinant proteins, we confirmed that bullous pemphigoid (BP) sera react with multiple epitopes on the BP230 molecule, particularly on the C-terminal region. In addition, to examine the specific reactivity of BP sera with BP230, we also examined the reactivity of non-BP sera with BP230 recombinant proteins by the same method. The 3 recombinant proteins were reacted very weakly by very few sera of non-BP patients. This result suggests that BP sera specifically react with BP230, although the pathogenic role of autoantibodies with BP 230 is still unclear.
By the similar method, we also obtained 3 recombinant GST fusion proteins, which covered the entire extracellular domain of BP180 as well as … More a recombinant protein of BP180 NC16a domain. Using immunoblotting of these recombinant proteins, we first confirmed that BP sera specifically react with NC16a domain in the N-terminal region of BP180. We also found that cicatricial pemphigoid sera contain IgG and IgA reactive with C-terminal region of BP180. In addition, the sera of linear IgA bullous dermatosis (LAD) of lamina lucida type seem to react with epitopes on the N-terminal region of BP180, which is a little distal to C-terminal, if compared to the epitope for BP.Therefore, we prepared an additional recombinant protein covering the 15th collagenous domain (C15) of BP180. Nearly half of LAD sera specifically reacted with this recombinant protein. This result suggests that at least some LAD sera contain IgA antibodies reactive with epitopes within C15 domain.
In addition, we established a novel ELISA using the recombinant protein of BP180 NC16a domain, and we are now examining many sera from various types of autoimmune bullous diseases to confirm the specificity of tthis new ELISA.These immunoblot and ELISA analyses using various different recombinant proteins of both BP180 and BP230 should be very important methods to obtain definite diagnoses for various autoimmune bullous dermatosis with anti-basement menbrane zone antibodies. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Hashimoto T et al: "Continuing Medical Education : The new pemphigus variants"J Am Acad Dermatol. 40. 649-671 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Complementary peptide against the major epitope in NCa6A of BP180 show no spidicificity as vaccines ot bulous pemphigoid"J Dermatol Sci. 21. 157-164 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A,Hashimoto T et al: "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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "IgA antibodies of cicatricial pemphigoid sera specifically react with C-terminus of BP180"J Invest Dermatol. 112. 254-255 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Paraneoplastic pemphigus with cutaneous and serological features of pemphigus foliaceus"Br J Dermatol. 141. 351-359 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A,Hashimoto T et al: "Sublamina densa-type linear IgA bullous dermatosis successively treated with oral tetracyclin and niacinamide"Br J Dermatol. 141. 608-609 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Unique immunobullous disease in a child with a predominantly IgA response to three desmosomal proteins"Br J Dermatol. 141. 882-886 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A,T.Hashimoto et al: "Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1"Br J Dermatol. 142. 143-147 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T,Komai A et al: "Bullous pemphigoid associated with silicosis"Dermatology. 201. 265-267 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin."J Am Acad Dermatol. 43. 923-926 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen"Br J Dermatol. 143. 1043-1049 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "IgA antibodies of linear IgA bullous dermatosis recognize the 15th collagenous domain of BP180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A,Hashimoto T et al: "Anti-desmoglein autoantibodies in silicosis patients with no bullous diseases"Dermatology,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid"J Dermatol Sci,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T,Komai A et al: "Immunopathological diagnosis of cicatricial pemphigoid with desquamative gigivitis-A case report"J Periodontology,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A,Hashimoto T et al: "The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay"Br J Dermatol,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T,Komai A et al: "Desmogleins are targeted by IgA autoantibodies of a few IgA pemphigus patients"Arch Dermatol,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering the entire molecule"Exp Dermatol,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Continuing Medical Education : The new pemphigus variants"J Am Acad Dermatol. 40. 649-671 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Complementary peptide against the major epitope in NCa6A of BP180 show no spidicificity as vaccines ot bulous pemphigoid"J Dermatol Sci. 21. 157-164 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A, Hashimoto T et al: "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
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "IgA antibodies of cicatricial pemphigoid sera specifically react with C-terminus of BP180"J Invest Dermatol. 112. 254-255 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Paraneoplastic pemphigus with cutaneous and serological features of pemphigus foliaceus"Br J Dermatol. 141. 351-359 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A, Hashimoto T et al: "Sublamina densa-type linear IgA bullous dermatosis successively treated with oral tetracyclin and niacinamide"Br J Dermatol. 141. 608-609 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Unique immunobullous disease in a child with a predominantly IgA response to three desmosomal proteins"Br J Dermatol. 141. 882-886 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A, Hashimoto T et al: "The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay"Br J Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T, Komai A et al: "Desmogleins are targeted by IgA autoantibodies of a few IgA pemphigus patients"Arch Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering the entire molecule"Exp Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A, Hashimoto T et al: "Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1"Br J Dermatol. 142. 143-147 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T, Komai A et al: "Bullous pemphigoid associated with silicosis"Dermatology. 201. 265-267 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin"J Am Acad Dermatol. 43. 923-926 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen"Br J Dermatol. 143. 1043-1049 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "IgA antibodies of linear IgA bullous dermatosis recognize the 15th collagenous domain of BP180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai A, Hashimoto T et al: "Anti-desmoglein autoantibodies in silicosis patients with no bullous diseases"Dermatology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid"J Dermatol Sci. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T, Komai A et al: "Immunopathological diagnosis of cicatricial pemphigoid with desquamative gigivitis - A case report"J Periodontology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto T et al: "Continuing Medical Education : The new pemphigus variants"J Am Acad Dermatol. 40. 649-671 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Complementary peptide against the major epitope in NCa6A of BP180 show no spidicificity as vaccines ot bulous pemphigoid"J Dermatol Sci. 21. 157-164 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,Hashimoto T et al: "Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus"Arch Dermatol. 135. 943-947 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "IgA antibodies of cicatricial pemphigoid sera specifically react with C-terminus of BP180"J Invest Dermatol. 112. 254-255 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Paraneoplastic pemphigus with cutaneous and serological features of pemphigus foliaceus"Br J Dermatol. 141. 351-359 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,Hashimoto T et al: "Sublamina densa-type linear IgA bullous dermatosis successively treated with oral tetracyclin and niacinamide"Br J Dermatol. 141. 608-609 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Unique immunobullous disease in a child with a predominantly IgA response to three desmosomal proteins"Br J Dermatol. 141. 882-886 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,T.Hashimoto et al: "Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1"Br J Dermatol. 142. 143-147 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T,Komai A et al: "Bullous pemphigoid associated with silicosis"Dermatology. 201. 265-267 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin."J Am Acad Dermatol. 43. 923-926 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen"Br J Dermatol. 143. 1043-1049 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "IgA antibodies of linear IgA bullous dermatosis recognize the 15th collagenous domain of BP180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,Hashimoto T et al: "Anti-desmoglein autoantibodies in silicosis patients with no bullous diseases"Dermatology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid"J Dermatol Sci. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T,Komai A et al: "Immunopathological diagnosis of cicatricial pemphigoid with desquamative gigivitis-A case report"J Periodontology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,Hashimoto T et al: "The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay"Br J Dermatol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T,Komai A et al: "Desmogleins are targeted by IgA autoantibodies of a few IgA pemphigus patients"Arch Dermatol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T et al: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analysis using bacterial recombinant proteins covering the entire molecule"Exp Dermatol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami H et al.: "Analysis of antigens targeted by circulating IgG and IgA antibodies in 50 patients with cicatricial pemphigoid"J Dermatol Sci. 17. 39-44 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirako Y et al.: "Cleavage of BP180 (Type XVII collagen) yields a 120 kDa collagenous extracellular peptide"J Biol Chem. 273(16). 9711-9717 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Chen LS et al: "Epitope spreading: lessons from autoimmune skin diseases"J Invest Dermatol. 110. 103-109 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nousari HC et al.: "The mechanism of respiratory failure in paraneoplastic pemphigus"N Eng J Med. 340. 1406-1410 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nie Z,Hashimoto T: "Complementary peptide a gainst the major epitope in NCa6A of BP180 show no spidicificity as vaccines ot bulous pemphigoid"J Dermatol Sci. 21. 157-164 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hashimoto T: "Skin diseases related to abnormality in desmosomes and hemidesmosomes"Dermatol Sci. 20. 81-84 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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