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Elucidation of the pathomechanism of anti-desmocollin antibodies in pemphigus

Research Project

Project/Area Number 19K08762
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKurume University

Principal Investigator

Koga Hiroshi  久留米大学, 医学部, 講師 (40461412)

Co-Investigator(Kenkyū-buntansha) TEYE KWESI  久留米大学, 付置研究所, 助教 (30599303)
石井 文人  久留米大学, 医学部, 准教授 (80330827)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords天疱瘡 / 腫瘍随伴性天疱瘡 / デスモコリン / 自己抗体 / カドヘリン
Outline of Research at the Start

天疱瘡は表皮細胞膜表面に対する自己抗体が血中に存在し、水疱を生じる自己免疫性疾患である。デスモグレイン(Dsg)に対する抗体が検出されることが知られており、その水疱形成機序については解明が進んでいる。一方、デスモコリン(Dsc)、特にDsc3に対する抗体も検出されるが、その病態への関与についてはまだ解明されていない点が多い。
本研究ではDsc3抗体の特徴を解析するため、Dsc3の細胞外配列を部分的に改変した蛋白を作製し、抗体の反応する部位、それによる病原性の違いについて解析を進める。

Outline of Final Research Achievements

This study was conducted to analyze the epitopes of anti-desmocollin (Dsc)3 in sera from the patients with pemphigus using Dsc3/desmoglein (Dsg)2 homologous recombinant proteins which are able to analyze antigen-antibody interactions on conformational epitopes. In results, the majority of anti-Dsc3 antibodies recognized extracellular (EC) 2 domain only when it constructed the conformational epitopes in the presence of calcium ions. Further experiments revealed that the Dsc3 antibodies recognized conformational EC2 domain exerted a reduction of Dsc3 expression on the cell surface of keratinocyte and an attenuation of adhesion of keratinocytes. This study revealed the characters of anti-Dsc3 antibodies in pemphigus patients.

Academic Significance and Societal Importance of the Research Achievements

従来、天疱瘡の研究は検出頻度の高い、Dsg3抗体について行われてきた。一方で、我々が示すようにDsc3抗体も一部の天疱瘡患者で検出され、病態に関与していることが考えられる。このようにDsc抗体に着目した通常とは異なるアプローチで研究を促進することは天疱瘡の病態解明、さらにはその他の自己免疫性疾患の病態解明にとって有益であると考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Autoantibodies to desmocollin 3 in pemphigus exclusively recognize calcium-dependent epitope in extracellular domain 22021

    • Author(s)
      Koga Hiroshi、Teye Kwesi、Otsuji Yoshihiko、Ishii Norito、Hashimoto Takashi、Nakama Takekuni
    • Journal Title

      Journal of Investigative Dermatology

      Volume: - Issue: 9 Pages: 2123-2131.e2

    • DOI

      10.1016/j.jid.2021.01.032

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Pemphigus autoantibodies to desmocollin 3 exclusively recognize calcium-dependent epitope in extracellular domain 22019

    • Author(s)
      Hiroshi Koga, Kwesi Teye, Norito Ishii, Takekuni Nakama
    • Organizer
      49th European Society for Dermatological Research Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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