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Clinical features and molecular pathology of anti-Lrp4 antibody-positive motor neuron disorders

Research Project

Project/Area Number 15K08636
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionNagasaki Kawatana Medical Center

Principal Investigator

Higuchi Osamu  独立行政法人国立病院機構長崎川棚医療センター(臨床研究部), その他の研究科, 研究員(移行) (50361720)

Co-Investigator(Kenkyū-buntansha) 瀬筒 秀樹  国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門, ユニット長 (70342805)
中根 俊成  熊本大学, 大学院生命科学研究部(医), 寄附講座教員 (70398022)
Research Collaborator 瀬筒 秀樹   (70342805)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsautoantobody / ALS / neuroimmunology / surrogatemarker / epitope / agrin / LRP4 / MG / エピトープ / 抗体 / 抗原 / 重症筋無力症 / 自己抗体 / 運動ニューロン / 神経変性疾患
Outline of Final Research Achievements

As a result of searching for LRP4 antibody in patient serum of amyotrophic lateral sclerosis (ALS) which is one of neurodegenerative diseases, LRP4 antibody was positive in 40-50% of cases. The inhibitory effect on agrin-induced AChR clustering activity in mouse myotube cells was examined. As a result, the serum of patients with LRP4 antibody positive myasthenia gravis had its inhibitory effect, but in sera of LRP4 antibody-positive ALS patients it I did not find it. It is speculated that the results of this study reflect the difference in the epitope of the disease-specific LRP4 antibody.
The LRP4 antibody found in the blood of ALS patients may be expected to play a role as a surrogate marker capable of tracking ALS onset and therapeutic responsiveness in the future.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (18 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (15 results) (of which Invited: 5 results)

  • [Journal Article] Double-seropositive myasthenia gravis with acetylcholine receptor and low-density lipoprotein receptor-related protein 4 antibodies associated with invasive thymoma.2017

    • Author(s)
      3.Ishikawa H, Taniguchi A, Ii Y, Higuchi O, Matsuo H, Nakane S, Asahi M, Niwa A, Tomimoto H.
    • Journal Title

      Neuromuscul Disord.

      Volume: 27 Issue: 10 Pages: 914-914

    • DOI

      10.1016/j.nmd.2017.06.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Double Seronegative Myasthenia Gravis with Anti-LRP4 Antibodies Presenting with Dropped Head and Acute Respiratory Insufficiency2016

    • Author(s)
      Beck G, Yabumoto T, Baba K, Sasaki T, Higuchi O, Matsuo H, Mochizuki H.
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 22 Pages: 3361-3363

    • DOI

      10.2169/internalmedicine.55.7030

    • NAID

      130005281922

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Myasthenic symptoms in anti-low-density lipoprotein receptor-related protein 4 antibody-seropositive amyotrophic lateral sclerosis: two case reports.2016

    • Author(s)
      Takahashi H, Noto YI, Makita N, Kushimura-Okada Y, Ishii R, Tanaka A, Ohara T, Nakane S, Higuchi O, Nakagawa M, Mizuno T
    • Journal Title

      BMC neurology

      Volume: 16 Issue: 1 Pages: 229-229

    • DOI

      10.1186/s12883-016-0758-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] LRP4抗体陽性患者5名の報告2018

    • Author(s)
      尾上祐行, 乗峯苑子, 小川知宏, 沼畑恭子, 吉澤健太, 赤岩靖久, 横田隆子, 樋口理, 松尾秀徳, 宮本智之
    • Organizer
      日本内科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] その後のLRP4抗体陽性筋無力症を考える2017

    • Author(s)
      中根俊成, 樋口理, 安東由喜雄
    • Organizer
      日本臨床神経生理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Agrinシグナル阻害抗体群が潜在する非古典的重症筋無力症2017

    • Author(s)
      樋口理
    • Organizer
      日本神経免疫学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] repetitive CMAPを認め,神経筋接合部の微細構造を解析し得た抗LRP4抗体陽性重症筋無力症の一例2017

    • Author(s)
      光武明彦, 平賢一郎, 荒川晶, 佐藤達哉, 勝又淳子, 関大成, 前川理沙, 日出山拓人, 石浦浩之, 内尾直裕, 清水潤, 樋口理, 松尾秀徳, 椎尾康
    • Organizer
      日本神経免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Luciferase immunoprecipitation systemsを用いた抗Muscle specific receptor tyrosin kinase抗体測定の確立2017

    • Author(s)
      前田泰宏, 前田泰宏, 樋口理, 中根俊成, 松尾秀徳, 松尾秀徳
    • Organizer
      日本神経免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋炎に好発するLRP4抗体2016

    • Author(s)
      樋口理
    • Organizer
      第8回筋炎ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2016-10-01
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 重症筋無力症に出現する自己抗体群の病態的意義2016

    • Author(s)
      樋口理
    • Organizer
      第28回日本神経免疫学会学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] LRP4抗体関連症候群2016

    • Author(s)
      樋口理
    • Organizer
      第57回日本神経学会学術大会2016@神戸
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 筋萎縮性側索硬化症患者おける抗LRP4抗体とその臨床像の検討2016

    • Author(s)
      前田泰宏・樋口 理,松尾秀徳
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 当院における抗 LRP4 抗体陽性重症筋無力症の臨床的特徴2016

    • Author(s)
      高松孝太郎1, 中根俊成1, 山川詩織1, 増田曜章1, 三隅洋平1, 軸丸美香1, 植田光晴1, 中島誠1, 石崎雅俊2, 樋口理3, 安東由喜雄1
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 抗AChR抗体と抗LRP4抗体の二重陽性を呈した浸潤性胸腺腫合併重症筋無力症2例の検討2016

    • Author(s)
      石川英洋1, 谷口彰1, 伊井裕一郎1, 樋口理2, 松尾秀徳3, 中根俊成4, 朝日理1, 丹羽篤1, 冨 本秀和1
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 重症筋無力症における抗MuSK抗体および抗Lrp4抗体と胸腺異常2016

    • Author(s)
      松尾秀徳1、樋口 理2、中根俊成3、前田泰宏1、成田智子1、酒井和香1
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
  • [Presentation] LRP4凝集体を認識する自己抗体の病態的意義2016

    • Author(s)
      樋口理・松尾秀徳
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2016-05-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 神経筋疾患スペクトラムに潜在する抗LRP4抗体2015

    • Author(s)
      樋口 理1,中根俊成2,前田泰宏3,鈴木秀和4,能登祐一5,安東由喜雄2,水野繁樹5,楠   進4,松尾秀徳3
    • Organizer
      第27回日本神経免疫学会学術集会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 抗AChR抗体、抗Lrp4抗体陽性であった運動ニューロン疾患と考えた1例2015

    • Author(s)
      前田泰宏1),2)、樋口理2)、酒井和香1)、権藤雄一郎1)、永石彰子1)、福留隆泰1)、中根俊成3)、松尾秀徳1)
    • Organizer
      第27回日本神経免疫学会学術集会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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