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identification of autoantigens of autoimmune pancreatitis

Research Project

Project/Area Number 21H02901
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKyoto University

Principal Investigator

Shiokawa Masahiro  京都大学, 医学研究科, 助教 (50737880)

Co-Investigator(Kenkyū-buntansha) 桑田 威  神戸大学, 医学研究科, 特別研究員(PD) (10879084)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords自己免疫性膵炎 / 自己抗体 / 自己抗原 / IgG4関連疾患 / IgG4 / IgG4関連疾患 / IgG4
Outline of Research at the Start

申請者らは、IgG4関連疾患の膵病変である自己免疫性膵炎AIPにおいて、その病因自己抗原がラミニン511であることを世界に先駆けて発見した(Sci Transl Med. 2018;10:453)。しかし、ラミニン511自己抗体は自己免疫性膵炎患者の約半数でしか陽性にならず、残りの自己抗体の同定が課題である。
本研究の目的は、ラミニン511以外のAIPの自己抗原を同定することである。

Outline of Final Research Achievements

We were the first in the world to discover that the causative autoantigen in autoimmune pancreatitis (AIP), a pancreatic lesion of IgG4-related disease, is laminin 511 (Sci Transl Med. 2018;10:453). However, laminin 511 autoantibodies are only positive in about half of autoimmune pancreatitis patients, and the identification of the remaining autoantibodies remains a challenge. In this study, autoantibodies against integrin α6β1, a protein that binds to laminin, were positive in about 20% of laminin 511 autoantibody-negative cases, and other studies have revealed that they are true autoantigens. Identification of the remaining 30% of autoantibodies remains a future challenge.

Academic Significance and Societal Importance of the Research Achievements

世界中でAIPを含めたIgG4関連疾患の病態と関連する自己抗原を同定しているグループは申請者のグループ以外には認めず、同研究は学術的独自性、重要性が非常に高い。今回新たに抗インテグリンα6β1自己抗体が病因抗体として検証できたことは、学術的に独創的かつ創造性に富む研究と言える。また、本抗体は診断・病勢評価にも使用し、将来的には治療ターゲットにもなると考えられ、実臨床への応用も十分に期待でき、社会的意義も大きいと考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (2 results)

All 2021

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

  • [Journal Article] Review of Diagnostic Biomarkers in Autoimmune Pancreatitis: Where Are We Now?2021

    • Author(s)
      Yokode M, Shiokawa M, Kodama Y.
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 5 Pages: 770-770

    • DOI

      10.3390/diagnostics11050770

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Antigens and autoantibodies in IgG4-RD: Laminin-511, Galectin-3, Annexin-11, and others2021

    • Author(s)
      Masahiro Shiokawa,Takeshi Kuwada, Sakiko Ota, Takeharu Nakamura, Hiroyuki Yoshida, Nobuyuki Kakiuchi, Saiko Marui, Yuko Sogabe, Toshihiro Morita, Tomoaki Matsumori, Atsushi Mima, Yoshihiro Nishikawa, Tatsuki Ueda, Norimitsu Uza, Kodama Yuzo Tsutomu Chiba, Hiroshi Seno
    • Organizer
      The 4th International Symposium on IgG4-related diseases The 13th Annual Meeting of Japanese Association of IgG4-related diseases
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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