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Clinical features of autoantibody-mediated small fiber neuropathy and developing novel neuropathic pain treatments using animal models

Research Project

Project/Area Number 21K15700
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionKyushu University

Principal Investigator

Fujii Takayuki  九州大学, 医学研究院, 助教 (30822481)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords神経障害性疼痛 / 小径線維ニューロパチー / 自己抗体 / 抗Plexin D1抗体
Outline of Research at the Start

小径線維ニューロパチー(SFN)は、神経障害性疼痛を主症状とし、その約半数は原因不明(特発性)で、しばしば難治である。近年、欧米諸国からは特発性SFNにおける自己抗体の存在が報告されており、感覚神経を標的とした自己抗体が特発性SFNの主要な原因である可能性が示唆されている。本研究では、特発性SFNにおいて自己抗体を測定し、陽性例の臨床的特徴を明らかにし、自己抗体を用いたSFNモデル動物の作成を行い、薬剤による感覚ニューロン活性化阻害の鎮痛効果を評価する。これにより、特発性SFNにおける自己抗体の関与を明らかにし、既存の免疫療法に加えて、分子標的治療薬を用いた新規治療法の開発につなげる。

Outline of Final Research Achievements

In this study, anti-Plexin D1 autoantibodies were detected in 15.8% of idiopathic small fiber neuropathy patients, who showed a high frequency of pricking pain and burning pain. Moreover, we focused on anti-Annexin A2 autoantibodies as a novel neuropathic pain related autoantibody.The frequency of anti-Annexin A2 autoantibodies was higher in patients with neuropathic pain than in healthy controls and patients without neuropathic pain. We have revealed the prevalence and clinucal features of autoantibody-mediated small fiber neuropathy and neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

小径線維ニューロパチーの原因の約半数は不明とされてきたが、本研究により抗Plexin D1抗体や抗Annexin A2抗体が小径線維ニューロパチーの新たな原因である可能性を示すことができた。原因不明の小径線維ニューロパチーにおいて、小径線維に結合する自己抗体を測定することにより原因を特定できる可能性がある。さらに、今後、自己抗体介在性ニューロパチーにおける免疫治療に対する効果が明らかとなった際には、これら自己抗体が免疫治療選択バイオマーカーとなる可能性がある。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (6 results) (of which Invited: 1 results) Book (1 results)

  • [Int'l Joint Research] Asan Medical Center(韓国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Anti-LGI4 antibody is a novel juxtaparanodal autoantibody for chronic inflammatory demyelinating polyneuropathy2023

    • Author(s)
      Zhang X, Kira J, Ogata H, Imamura T, Mitsuishi M, Fujii T, Kobayashi M, Kitagawa K, Namihira Y, Ohya Y, Maimaitijiang G, Yamasaki R, Fukata Y, Fukata M, Isobe N, Nakamura Y.
    • Journal Title

      Neurology Neuroimmunology and Neuroinflammation

      Volume: 10(2) Issue: 2 Pages: 1-13

    • DOI

      10.1212/nxi.0000000000200081

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-Plexin D1 antibodies relate to small fiber neuropathy and induce neuropathic pain in animals.2021

    • Author(s)
      Fujii T, Lee E-J, Miyachi Y, Yamasaki R, Lim Y-M, Iinuma K, Sakoda A, Kim K-K, Kira J:
    • Journal Title

      Neurology: Neuroimmunology & Neuroinflammation

      Volume: 8(5) Issue: 5

    • DOI

      10.1212/nxi.0000000000001028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum anti-oligodendrocyte autoantibodies in patients with multiple sclerosis detected by a tissue-based immunofluorescence assay2021

    • Author(s)
      Miyachi Y, Fujii T, Yamasaki R, Tsuchimoto D, Iinuma K, Sakoda A, Fukumoto S, Matsushita T, Masaki K, Isobe N, Nakabeppu Y, Kira J.
    • Journal Title

      Front Neurol

      Volume: 12 Pages: 681980-681980

    • DOI

      10.3389/fneur.2021.681980

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 自己抗体介在性小径線維ニューロパチー2021

    • Author(s)
      藤井敬之、山﨑亮
    • Journal Title

      末梢神経

      Volume: 32 Pages: 31-37

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Plexin D1 is upregulated in degenerated motor neurons of amyotrophic lateral sclerosis patients2022

    • Author(s)
      Takayuki Fujii, Hiroyuki Honda, Ryo Yamasaki, Motoi Yoshimura, Toru Iwaki, Noriko Isobe
    • Organizer
      63rd Annual Meeting of the Japanese Society of Neurology
    • Related Report
      2022 Annual Research Report
  • [Presentation] SEMA 3E-Plexin D1経路に着目した筋萎縮性側索硬化症の病態解明2022

    • Author(s)
      藤井敬之、本田裕之、山﨑亮、吉村基、岩城徹、磯部紀子
    • Organizer
      第119回日本内科学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 定量的感覚検査を用いた自己免疫性ノドパチーにおける 小径線維障害の検討2022

    • Author(s)
      藤井敬之、緒方英紀、山﨑亮、磯部紀子
    • Organizer
      第34回日本神経免疫学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Autoantibody-related neuropathic pain2022

    • Author(s)
      Takayuki Fujii
    • Organizer
      The 96th Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] The clinical features of small fiber neuropathy patients with anti-Plexin D1 antibodies2021

    • Author(s)
      Takayuki Fujii, Ryo Yamasaki, Yukino Miyachi, Kyoko Iinuma, Ayako Sakoda, Eun-Jae Lee, Young-Min Lim, Kwang-kuk Kim, Jun-ichi Kira, Noriko Isobe
    • Organizer
      62nd Annual Meeting of the Japanese Society of Neurology
    • Related Report
      2021 Research-status Report
  • [Presentation] 間接蛍光抗体法による多発性硬化症患者血清中の 抗オリゴデンドロサイト抗体の検討2021

    • Author(s)
      藤井 敬之、宮地 佑希野、山﨑 亮 、土本 大介、迫田 礼子、福元 尚子、松下 拓也、中別府 雄作、吉良 潤一、磯部 紀子
    • Organizer
      第33回日本神経免疫学会学術集会
    • Related Report
      2021 Research-status Report
  • [Book] Annual review 神経 20222022

    • Author(s)
      藤井敬之、宮地佑希野
    • Total Pages
      5
    • Publisher
      中外医学社
    • Related Report
      2022 Annual Research Report 2021 Research-status Report

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Published: 2021-04-28   Modified: 2024-01-30  

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