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Evaluation of alterations in post-translational modification of autoantigens as a novel early phase diagnostic marker for ANCA associated vasculitis.

Research Project

Project/Area Number 17K08998
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionKindai University

Principal Investigator

Nagai Kouhei  近畿大学, 生物理工学部, 准教授 (70500578)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords自己免疫疾患 / ANCA関連血管炎 / 自己抗原 / 翻訳後修飾 / 膠原病 / 質量分析 / 血管炎 / 診断マーカー / 翻訳語修飾 / 免疫学 / 蛋白質 / プロテオーム
Outline of Final Research Achievements

In this study, we analyzed post-translational modifications (PTMs) of autoantigen Myeloperoxinase (MPO) in peripheral blood neutrophils from patients with ANCA-related vasculitis. Neutrophil MPO was purified from peripheral blood of 8 patients with ANCA-related vasculitis and 8 healthy controls, digested with trypsin, and analyzed by high-performance LC-MS. Database search against human proteome database identified 52 PTMs on the MPO molecules. Among them, multiple post-translational modifications such as Carbamylation were significantly increased in the patient group. Furthermore, the immunization of mice with a post-translational modification-introduced mouse protein causes a temporary increase in the antibody titer against the self-protein. These results indicated the relationship between abnormal post-translational modification and autoantibody production.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ANCA関連血管炎患者の体内の自己抗原タンパク質Myeloperoxidase(MPO)上に、患者特異的な翻訳後修飾が存在することを初めて示した。更に、自己タンパク質の翻訳後修飾の異常が自己抗体を誘導しうることをマウスを用いた実験により示した。本研究成果は、ANCA関連血管炎における疾患発症機序の解明に寄与するだけでなく、MPOにおける患者特異的翻訳後修飾が、自己抗体の産生に先駆ける現象として、ANCA関連血管炎の早期診断マーカーとして使用できる可能性を示したということで大きな社会的意義を有していると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2019 2017

All Presentation (2 results)

  • [Presentation] ANCA関連血管炎患者における自己抗原Myeloperoxidaseの翻訳後修飾の解析2019

    • Author(s)
      佐々木琳子, 永井宏平, 西端智也, 佐藤政秋, 佐藤利行, 黒川真奈絵, 加藤智啓
    • Organizer
      日本プロテオーム学会2019年大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification and quantification of oxidative modifications that shifts isoelectric point of neutrophil myeloperoxidase2017

    • Author(s)
      Akane Hashimoto, Yutaro Onoue, Yukiko Jyogu , Megu Nishino , Manae S. Kurokawa, Tomohiro Kato, Kouhei Nagai
    • Organizer
      ConBIO2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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