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Development of diagnostic tools and discovery of pathology in anti-MOG antibody associated demyelinating disease

Research Project

Project/Area Number 17K09772
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTohoku Medical and Pharmaceutical University (2018-2019)
Tohoku University (2017)

Principal Investigator

Nakashima Ichiro  東北医科薬科大学, 医学部, 教授 (50333810)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords脱髄疾患 / 多発性硬化症 / 視神経脊髄炎 / 自己抗体 / 脳神経疾患
Outline of Final Research Achievements

To develop a new method for measuring anti-MOG antibodies, we established a system for measuring anti-MOG antibodies in the serum of patients with inflammatory demyelinating diseases using MOG-transfected HEK293 cells. We reported the clinical characteristics of cases with positive anti-MOG antibodies to establish the disease entity. We tried to develop a simple ELISA method for HEK293 cells, but the sensitivity was not sufficient because of the non-specific response against HEK293 cells as the antigen. To elucidate the pathogenesis of anti-MOG antibodies, we measured antibody titers in CSF during the acute phase of the disease and compared them with clinical symptoms. Pathological analysis was performed using biopsy brain specimens of anti-MOG antibody-positive inflammatory demyelinating disease collected from 11 cases.

Academic Significance and Societal Importance of the Research Achievements

抗MOG抗体が関与する中枢神経の脱髄疾患は、従来多発性硬化症あるいは視神経脊髄炎や急性散在性脳脊髄炎の病名で診断され、治療を受けていたが、本研究により多発性硬化症や視神経脊髄炎とは異なる病態を持つ疾患で新たな疾患概念として捉える必要があることが明確になった。
疾患予後や臨床所見は多発性硬化症に近いことが多いものの、免疫病態は視神経脊髄炎に類似しており、病理学的には急性散在性脳脊髄炎の特徴を有していた。新たな疾患概念の確立に非常に有用な知見を多く示すことが出来た。

Report

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

    (31 results)

All 2020 2019 2018 2017

All Journal Article (24 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 23 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Refractory case of myelin oligodendrocyte glycoprotein antibody‐associated encephalomyelitis with lumbosacral radiculitis2020

    • Author(s)
      Nakamura Masashi、Fujimori Juichi、Kobayashi Michiko、Ishigaki Aya、Kikuchi Hirokazu、Miyazawa Koichi、Sato Kazuhiko、Kawasaski Emiko、Suzuki Yasushi、Nakashima Ichiro
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: - Issue: 2 Pages: 126-130

    • DOI

      10.1111/cen3.12564

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Linear pontine trigeminal root lesion in a patient with anti‐myelin oligodendrocyte glycoprotein antibody‐associated encephalitis2020

    • Author(s)
      Fujimori Juichi、Nakashima Ichiro
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: - Issue: 2 Pages: 122-125

    • DOI

      10.1111/cen3.12555

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term outcome of a group of Japanese children with myelin-oligodendrocyte glycoprotein encephalomyelitis without preventive immunosuppressive therapy2019

    • Author(s)
      Hino-Fukuyo N, Haginoya K, Takahashi T, Nakashima I, Fujihara K, Takai Y, Akasaka M, Kure S
    • Journal Title

      Brain Dev

      Volume: 41 Issue: 9 Pages: 790-795

    • DOI

      10.1016/j.braindev.2019.06.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two Japanese cases of anti-MOG antibody-associated encephalitis that mimicked neuro-Behçet's disease.2019

    • Author(s)
      Fujimori J, Takahashi T, Matsumoto Y, Fujihara K, Takai Y, Misu T, Nakashima I.
    • Journal Title

      J Neuroimmunol

      Volume: 334 Pages: 577002-577002

    • DOI

      10.1016/j.jneuroim.2019.577002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live-cell based assays are the gold standard for anti-MOG-Ab testing2019

    • Author(s)
      Yeh E. Ann、Nakashima Ichiro
    • Journal Title

      Neurology

      Volume: 92 Issue: 11 Pages: 501-502

    • DOI

      10.1212/wnl.0000000000007077

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Orexin secretion abnormality involved in excessive somnolence in CNS lymphoma without hypothalamic lesions.2019

    • Author(s)
      Hamada Y, Takata T, Kawakita R, Kobara H, Okada M, Tamiya T, Kanbayashi T, Touge T, Deguchi K, Masaki T.
    • Journal Title

      J Clin Neurosci

      Volume: S0967-5868 Pages: 30421-30427

    • DOI

      10.1016/j.msard.2018.12.035

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical spectrum of inflammatory central nervous system demyelinating disorders associated with antibodies against myelin oligodendrocyte glycoprotein2019

    • Author(s)
      Akaishi Tetsuya、Sato Douglas Kazutoshi、Takahashi Toshiyuki、Nakashima Ichiro
    • Journal Title

      Neurochemistry International

      Volume: 130 Pages: 104319-104319

    • DOI

      10.1016/j.neuint.2018.10.016

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebellar lesions in a patient with anti‐myelin oligodendrocyte glycoprotein antibody‐associated encephalitis2019

    • Author(s)
      Fujimori Juichi、Nakashima Ichiro
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: 10 Issue: 4 Pages: 264-266

    • DOI

      10.1111/cen3.12539

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical time course of pediatric acute disseminated encephalomyelitis2019

    • Author(s)
      Nishiyama Masahiro、Nagase Hiroaki、Tomioka Kazumi、Tanaka Tsukasa、Yamaguchi Hiroshi、Ishida Yusuke、Toyoshima Daisaku、Fujita Kyoko、Maruyama Azusa、Sasaki Kaori、Oyazato Yoshinobu、Nakagawa Taku、Takami Yuichi、Nozu Kandai、Nishimura Noriyuki、Nakashima Ichiro、Iijima Kazumoto
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 6 Pages: 531-537

    • DOI

      10.1016/j.braindev.2019.02.011

    • NAID

      120006645705

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myelin Oligodendrocyte Glycoprotein-IgG-positive Recurrent Bilateral Optic Papillitis with Serous Retinal Detachment2018

    • Author(s)
      Kon Tomoya、Hikichi Hiroki、Ueno Tatsuya、Suzuki Chieko、Nunomura Jinichi、Kaneko Kimihiko、Takahashi Toshiyuki、Nakashima Ichiro、Tomiyama Masahiko
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 22 Pages: 3307-3312

    • DOI

      10.2169/internalmedicine.9840-17

    • NAID

      130007511604

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-11-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat2018

    • Author(s)
      Hillebrand Sophie、Schanda Kathrin、Nigritinou Magdalini、Tsymala Irina、Boehm Denise、Peschl Patrick、Takai Yoshiki、Fujihara Kazuo、Nakashima Ichiro、Misu Tatsuro、Reindl Markus、Lassmann Hans、Bradl Monika
    • Journal Title

      Acta Neuropathologica

      Volume: 137 Issue: 3 Pages: 467-485

    • DOI

      10.1007/s00401-018-1950-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MOG-IgG-associated disease has a stereotypical clinical course, asymptomatic visual impairment and good treatment response2018

    • Author(s)
      Pandit Lekha、Mustafa Sharik、Nakashima Ichiro、Takahashi Toshyuki、Kaneko Kimhiko
    • Journal Title

      Multiple Sclerosis Journal - Experimental, Translational and Clinical

      Volume: 4 Issue: 3 Pages: 1-9

    • DOI

      10.1177/2055217318787829

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications2018

    • Author(s)
      Kaneko Kimihiko、Sato Douglas Kazutoshi、Nakashima Ichiro、Ogawa Ryo、Akaishi Tetsuya、Takai Yoshiki、Nishiyama Shuhei、Takahashi Toshiyuki、Misu Tatsuro、Kuroda Hiroshi、Tanaka Satoru、Nomura Kyoichi、Hashimoto Yuji、Callegaro Dagoberto、Steinman Lawrence、Fujihara Kazuo、Aoki Masashi
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 89 Issue: 9 Pages: 927-936

    • DOI

      10.1136/jnnp-2018-317969

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis2018

    • Author(s)
      Touil Hanane、for the Canadian B Cell Team in MS、Kobert Antonia、Lebeurrier Nathalie、Rieger Aja、Saikali Philippe、Lambert Caroline、Fawaz Lama、Moore Craig S.、Prat Alexandre、Gommerman Jennifer、Antel Jack P.、Itoyama Yasuto、Nakashima Ichiro、Bar-Or Amit
    • Journal Title

      Journal of Neuroinflammation

      Volume: 15 Issue: 1 Pages: 114-114

    • DOI

      10.1186/s12974-018-1136-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rituximab was effective for acute disseminated encephalomyelitis followed by recurrent optic neuritis with anti-myelin oligodendrocyte glycoprotein antibodies2018

    • Author(s)
      Nagashima Masako、Osaka Hitoshi、Ikeda Takahiro、Matsumoto Ayumi、Miyauchi Akihiko、Kaneko Kimihiko、Nakashima Ichiro、Nakano Yuko、Wakabayashi Kei、Monden Yukifumi、Yamagata Takanori
    • Journal Title

      Brain and Development

      Volume: 40 Issue: 7 Pages: 607-611

    • DOI

      10.1016/j.braindev.2018.03.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chloride imbalance is involved in the pathogenesis of optic neuritis in neuromyelitis optica2018

    • Author(s)
      Akaishi Tetsuya、Takahashi Toshiyuki、Himori Noriko、Takeshita Takayuki、Nakazawa Toru、Aoki Masashi、Nakashima Ichiro
    • Journal Title

      Journal of Neuroimmunology

      Volume: 320 Pages: 98-100

    • DOI

      10.1016/j.jneuroim.2018.03.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three Japanese adult cases of brain lesions with anti-myelin oligodendrocyte glycoprotein antibodies lacking optic neuritis and myelitis2018

    • Author(s)
      Sawada Jun、Katayama Takayuki、Toyoshima Sarasa、Nitamizu Senri、Yamamoto Kenji、Fukuura Ai、Kikuchi Shiori、Kano Kohei、Asanome Asuka、Takahashi Kae、Saito Tsukasa、Takahashi Toshiyuki、Kaneko Kimihiko、Nakashima Ichiro、Hasebe Naoyuki
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: 9 Issue: 3 Pages: 162-168

    • DOI

      10.1111/cen3.12459

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] MOG-IgG-associated disease: an overview2018

    • Author(s)
      Fujihara K, Sato DK, Nakashima I, Takahashi T, Kaneko K, Ogawa R, Akaishi T, Matsumoto Y, Takai Y, Nishiyama S, Kuroda H, Misu T, Aoki M.
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 9(Suppl.1) Issue: S1 Pages: 48-55

    • DOI

      10.1111/cen3.12434

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reversible paraspinal muscle hyperintensity in anti-MOG antibody-associated transverse myelitis.2017

    • Author(s)
      Pandit L, Mustafa S, Uppoor R, Nakashima I, Takahashi T, Kaneko K.
    • Journal Title

      Neurol Neuroimmunol Neuroinflamm

      Volume: 5 Issue: 1

    • DOI

      10.1212/nxi.0000000000000412

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti Myelin Oligodendrocyte Glycoprotein associated Immunoglobulin G (AntiMOG-IgG)-associated Neuromyelitis Optica Spectrum Disorder with Persistent Disease Activity and Residual Cognitive Impairment.2017

    • Author(s)
      Pandit L, Nakashima I, Mustafa S, Takahashi T, Kaneko K.
    • Journal Title

      Ann Indian Acad Neurol

      Volume: 20 Issue: 4 Pages: 411-413

    • DOI

      10.4103/aian.aian_250_17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A case of MOG antibody-positive bilateral optic neuritis and meningoganglionitis following a genital herpes simplex virus infection2017

    • Author(s)
      Nakamura Masataka、Iwasaki Yuko、Takahashi Toshiyuki、Kaneko Kimihiko、Nakashima Ichiro、Kunieda Takenobu、Kaneko Satoshi、Kusaka Hirofumi
    • Journal Title

      Mult Scler Relat Disord

      Volume: 17 Pages: 148-150

    • DOI

      10.1016/j.msard.2017.07.023

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Is MOG-IgG another biomarker for neuromyelitis optica?2017

    • Author(s)
      Nakashima Ichiro
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 88 Issue: 10 Pages: 807-807

    • DOI

      10.1136/jnnp-2017-316247

    • Related Report
      2017 Research-status Report
  • [Journal Article] Clinical features in very early-onset demyelinating disease with anti-MOG antibody2017

    • Author(s)
      Nishiyama Masahiro、Nagase Hiroaki、Matsumoto Masaaki、Tomioka Kazumi、Awano Hiroyuki、Tanaka Tsukasa、Toyoshima Daisaku、Fujita Kyoko、Maruyama Azusa、Oyazato Yoshinobu、Saeki Keisuke、Shiraishi Kazuhiro、Takada Satoshi、Kaneko Kimihiko、Takahashi Toshiyuki、Nakashima Ichiro、Iijima Kazumoto
    • Journal Title

      Brain Dev

      Volume: 39 Issue: 9 Pages: 756-762

    • DOI

      10.1016/j.braindev.2017.05.004

    • NAID

      120006599196

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection2017

    • Author(s)
      Nakamura Y, Nakajima H, Tani H, Hosokawa T, Ishida S, Kimura F, Kaneko K, Takahashi T, Nakashima I.
    • Journal Title

      BMC Neurol

      Volume: 17 Issue: 1 Pages: 76-76

    • DOI

      10.1186/s12883-017-0858-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 抗MOG抗体関連疾患2019

    • Author(s)
      中島一郎
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Case-based Considerations in Clinical Practice for MOG Antibody Associated Disease2018

    • Author(s)
      Ichiro Nakashima
    • Organizer
      16th Asian Oceanian Congress of Neurology
    • Related Report
      2018 Research-status Report
  • [Presentation] Clinical Aspects of MOG-IgG Related Demyelinating Diseases2018

    • Author(s)
      Ichiro Nakashima
    • Organizer
      The Hong Kong Multiple Sclerosis Society Annual Scientific Meeting
    • Related Report
      2018 Research-status Report
  • [Presentation] 視神経脊髄炎関連疾患2018

    • Author(s)
      中島一郎
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] MOG抗体関連脱髄疾患2018

    • Author(s)
      中島一郎
    • Organizer
      第36回日本神経治療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗AQP4抗体関連疾患と抗MOG抗体関連疾患2017

    • Author(s)
      中島一郎
    • Organizer
      第59回日本小児神経学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Mechanism and spectrum of MOG antibody-mediated encephalomyelitis2017

    • Author(s)
      Ichiro Nakashima
    • Organizer
      Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (PACTRIMS) 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited

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

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