Clinical and Pathophysiological analysis of myelin Oligodendrocyte Glycoprotein antibody-Associated Neurologic Disease

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17H04192
• Research Institution: Tohoku University
• Principal Investigator: 藤原 一男 東北大学, 医学系研究科, 大学院非常勤講師 (70280873)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ミエリンオリゴデンドロサイト糖タンパク / 脱髄疾患 / 自己抗体 / 自己免疫性脳炎

Outline of Annual Research Achievements

昨年に引き続きミエリンオリゴデンドロサイト糖タンパク(MOG)抗体陽性神経疾患の臨床・病態・治療の解析を継続した。
1) MOG抗体陽性11例の脳生検の神経病理学的解析を行った。その結果、脱髄のパターンはperivenous demyelinationが大部分を占め、多発性硬化症(MS)で見られるconfluent demyelinationはまれであった。またアクアポリン4抗体陽性視神経脊髄炎と比較して、組織への活性化補体の沈着は低頻度だった。MOGの選手句の欠失はたのミエリンタンパクのそれより広範囲で、本疾患においてMOGがより選択的に障害されていることが示唆された。病変に浸潤しているリンパ球はCD4優位であり、MSのCD8優位のリンパ球浸潤と異なっていた。以上から、MOG抗体陽性神経疾患は、MSとは異なる炎症性脱髄疾患であると考えられた。本研究はBrainにacceptされた。
2)初発例の追跡調査により2年後までの再発率は約50%であることを見出した。なお大脳皮質脳炎は大部分の症例が初発時に起こっていた。
3)小児例では、一部にMSと診断されインターフェロンベーターなどのMS治療薬を投与されている症例があったが、再発予防効果はほとんどの症例ではみられなかった。本疾患では、アクアポリン4抗体陽性視神経脊髄炎と同様にMS治療薬が無効と思われた。
4)視神経脊髄炎症例において、アクアポリン4抗体陽性例ではsatralizumab (抗IL6受容体), inebilizumab (抗CD19)が再発予防に有効であることを、それぞれN Engl J Med, Lancetに報告したが、一部のアクアポリン4抗体陰性例(その一部はMOG抗体陽性)では再発予防効果は明らかではなかった。この事実は本疾患がアクアポリン4抗体陽性視神経脊髄炎と異なる治療反応性を呈することを示唆している。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Oxford(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: University of Oxford
• [Int'l Joint Research] Mayo Clinic/University of California San Fransisco/Johns Hopkins University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Mayo Clinic/University of California San Fransisco/Johns Hopkins University
• [Int'l Joint Research] National Cancer Center(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: National Cancer Center
• [Int'l Joint Research] Ruhr University Bochum/Charite Universitatsmedizin Berlin/Heinrich Heine University(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: Ruhr University Bochum/Charite Universitatsmedizin Berlin/Heinrich Heine University
• [Int'l Joint Research] Lyon University Hospital/INSERM(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: Lyon University Hospital/INSERM
• [Int'l Joint Research]
  • # of Other Countries: 5
• [Journal Article] Repeated follow-up of AQP4-IgG titer by cell-based assay in neuromyelitis optica spectrum disorders (NMOSD) (2020)
  • Author(s): Akaishi T, Takahashi T, Nakashima I, Abe M, Ishii T, Aoki M, Fujihara K
  • Journal Title: J Neurol Sci Volume: 410 Pages: 116671
  • DOI: 10.1016/j.jns.2020.116671
  • Peer Reviewed
• [Journal Article] Serum AQP4-IgG level is associated with the phenotype of thefirst attack inneuromyelitis optica spectrum disorders (2020)
  • Author(s): Akaishia T, Takahashia T, Himorid N, Fujiharae K, Misu T, Abe M, Ishii T, Nakazawa T, Aoki M, Nakashima I
  • Journal Title: J Neuroimmunol Volume: 344 Pages: 577168
  • DOI: 10.1016/j.jneuroim.2020.577168.
  • Peer Reviewed
• [Journal Article] Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study (2020)
  • Author(s): Takai Y, Misu T, Kaneko K, Chihara N, Narikawa K, Tsuchida S, Nishida H, Komori T, Seki M, Komatsu T, Nakamagoe K, Ikeda T, Yoshida M, Takahashi T, Ono H, Nishiyama S, Kuroda H, Nakashima I, Suzuki H, Bradl M, Lassmann H, Fujihara K, Aoki M
  • Journal Title: Brain Volume: 143 Pages: 1431-1446
  • DOI: 10.1093/brain/awaa102
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD (2020)
  • Author(s): Kleerekooper I, Herbert MK, Kuiperij HB, Sato DK, Fujihara K, Callegaro D, Marignier R, Saiz A, Senel M, Tumani H, de Jong BA, Trip SA, Nakashima I, Verbeek MM, Petzold A
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 91 Pages: 605-611
  • DOI: 10.1136/jnnp-2019-322286
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Perivenous demyelinaton: association with anti-myelin oligodendrocyte glycoprotein antibody (2020)
  • Author(s): Misu T. Takai Y, Takahashi T, Nakashima I, Fujihara K, Aoki M
  • Journal Title: Clin Exp Neuroimmunol Volume: 11(Suppl 1) Pages: 22-;27
  • DOI: 10.1111/cen3.12569
  • Peer Reviewed / Open Access
• [Journal Article] MOG-IgG-associated diseas (2020)
  • Author(s): Kaneko K, Takahahi T, Misu T, Nakashima I, Fujihara K
  • Journal Title: Clin Exp Neuroimmunol Volume: 11(Suppll 1) Pages: 28-33
  • DOI: 10.1111/cen3.12578
  • Peer Reviewed / Open Access
• [Journal Article] Trial of eculizumab in aquaporin-4 positive neuromyelitis optica spectrum disorder (2019)
  • Author(s): Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM
  • Journal Title: N Engl J Med Volume: 381 Pages: 614-625
  • DOI: 10.1056/NEJMoa1900866.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Long-term outcome of a group of Japanese children with myelin-oligodendrocyte glycoprotein encephalomyelitis without preventive immunosuppressive therapy (2019)
  • 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 Pages: 790-795
  • DOI: 10.1016/j.braindev.2019.06.004
  • 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
  • DOI: 10.1016/j.jneuroim.2019.577002.
  • Peer Reviewed
• [Journal Article] A randomised, placebo-controlled, double-blind trial of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: results of the N-MOmentum study (2019)
  • Author(s): Cree B, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E
  • Journal Title: Lancet Volume: 394 Pages: 1352-1363
  • DOI: 10.1016/S0140-6736(19)31817-3.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Trila of satralizumab in neuromyelitis optica spectrum disorder (2019)
  • Author(s): Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J
  • Journal Title: N Engl J Med Volume: 381 Pages: 2114-2124
  • DOI: 10.1056/NEJMoa1901747
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Regional brain volume losses and the patterns in multiple sclerosis; a cluster analysis (2019)
  • Author(s): Fujimori J, Fujihara K, Ogawa R, Baba T, Wattjes M, Nakashima I
  • Journal Title: J Neurol Volume: 267 Pages: 395-405
  • DOI: 10.1007/s00415-019-09595-4.
  • Peer Reviewed
• [Journal Article] NMO spectrum and MOG-antibody-related disseminated encephalomyelitis (2019)
  • Author(s): Misu T, Fujihara K
  • Journal Title: Clin Exp Neuroimmunol Volume: 10 Pages: 9-17
  • DOI: 10.1111/cen3.12491
  • Peer Reviewed / Open Access
• [Journal Article] Neuromyelitis optica spectrum disorders: still evolving and broadening. (2019)
  • Author(s): Fujihara K.
  • Journal Title: Curr Opin Neurol Volume: 32 Pages: 385-394
  • DOI: 10.1097/WCO.0000000000000694.
  • Peer Reviewed / Open Access
• [Presentation] There are cognitive deficits in non-brain NMOSD, NO (2020)
  • Author(s): Fujihara K
  • Organizer: European NMO Meeting 2020. Berlin (Germany)
  • Int'l Joint Research / Invited
• [Presentation] Charcot Lecture: NMO/NMOSD and anti-MOG related CNS Demyelinating Diseases. (2019)
  • Author(s): Fujihara K
  • Organizer: 54th Canadian Neurological Sciences Federation Congress, Montreal (Canada)
  • Int'l Joint Research / Invited
• [Presentation] Diagnosis of NMOSD (2019)
  • Author(s): Fujihara K
  • Organizer: Symposium of Neuroimmunology, Beijing (China)
  • Int'l Joint Research / Invited
• [Presentation] Update on NMOSD and MOG-IgG+disease (2019)
  • Author(s): Fujihara K
  • Organizer: The 5th Neuroimmunology and Neurological Infections Conference (NIC) and China Neuroimmunology Congress, Beijing (China))
  • Int'l Joint Research / Invited
• [Presentation] The differential diagnosis; NMOSD, MS, and anti-MOG (2019)
  • Author(s): Fujihara K
  • Organizer: 5th Indian Committee for Treatment and Research in Multiple Sclerosis (ICTRIMS), Kolkata (India)
  • Int'l Joint Research / Invited
• [Presentation] (Professor BS Singhal Oration): Spectrum of NMO: new developments and challenges (2019)
  • Author(s): Fujihara K
  • Organizer: 5th Indian Committee for Treatment and Research in Multiple Sclerosis (ICTRIMS), Kolkata (India),
  • Int'l Joint Research / Invited
• [Presentation] NMOSD: epidemiology update (2019)
  • Author(s): Fujihara K, hor JY
  • Organizer: 20th Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS), Sao Paulo (Brazil)
  • Int'l Joint Research / Invited
• [Presentation] Remyelination, a possible outcome: New endpoints in clinical trials for MS: remyelination, clinical improvement and more (2019)
  • Author(s): Fujihara K
  • Organizer: 20th Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS), Sao Paulo (Brazil)
  • Int'l Joint Research / Invited
• [Presentation] Neuropathological findings of MOG-antibody-associated disease (2019)
  • Author(s): Fujihara K
  • Organizer: 20th Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS), Sao Paulo (Brazil),
  • Int'l Joint Research / Invited
• [Presentation] Treatment of NMOSD (2019)
  • Author(s): Fujihara K
  • Organizer: 20th Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS), Sao Paulo (Brazil)
  • Int'l Joint Research / Invited
• [Presentation] Demyelinating Disease: MS, NMOSD and MOG-antibody-associated disease (2019)
  • Author(s): Fujihara K
  • Organizer: AIMS Neuro Imaging 2019, Tokyo (Japan),
  • Int'l Joint Research / Invited
• [Presentation] (Plenary Lecture) An introduction to CNS inflammatory demyelinating disorders (2019)
  • Author(s): Fujihara K
  • Organizer: 1st Sri Lankan Committee for Treatment and Research in Multiple Sclerosis (SLCTRIMS) Congress. Colombo (Sri Lanka),
  • Int'l Joint Research / Invited
• [Presentation] New Diagnostic Criteria for MS, a way forward (2019)
  • Author(s): Fujihara K
  • Organizer: 1st Sri Lankan Committee for Treatment and Research in Multiple Sclerosis (SLCTRIMS) Congress. Colombo (Sri Lanka),
  • Int'l Joint Research / Invited
• [Presentation] NMO spectrum disorders: from diagnosis to treatment. (2019)
  • Author(s): Fujihara K
  • Organizer: 1st Sri Lankan Commitee for Treatment and Research in Multiple Sclerosis (SLCTRIMS) Congress. Colombo (Sri Lanka)
  • Int'l Joint Research / Invited
• [Presentation] An approach to chronic inflammatory optic neuropathy (CRION) (2019)
  • Author(s): Fujihara K
  • Organizer: 1st Sri Lankan Committee for Treatment and Research in Multiple Sclerosis (SLCTRIMS) Congress. Colombo (Sri Lanka),
  • Int'l Joint Research / Invited
• [Presentation] MOG-antibody-associated disease (2019)
  • Author(s): Fujihara K
  • Organizer: Tiantian Neuroinfection & Neuroimmunology Forum (TNNF) 2019 Chinese Medical Network for Neuroinflammation (CMNN) 2019. Beijing (China),
  • Int'l Joint Research / Invited
• [Presentation] (Main Topic 5A: MS AND DEMYELINATING DISORDERS) IS AN INTERNATIONAL CONSENSUS POSSIBLE?. (2019)
  • Author(s): Fujihara K
  • Organizer: World Congress of Neurology 2019. Dubai (UAE)
  • Int'l Joint Research / Invited
• [Presentation] NMO and MOG-SD (2019)
  • Author(s): Fujihara K
  • Organizer: Istanbul MS Days 2019, Istanbul (Turkey)
  • Int'l Joint Research / Invited
• [Presentation] Biomarkers and Diagnosis of MS and NMOSD L-20) Lumpers and splitters in NMOSD: Does it matter? (2019)
  • Author(s): Fujihara K
  • Organizer: 12th Pan-Asian Committee for Treatment and Research in Multiple Sclerosisi (PACTRIMS), Singapore,
  • Int'l Joint Research / Invited
• [Presentation] Role of Pathogenic Antibodies. The Example of MOG Antibody Associated IDD) From Immunology to Treatment (2019)
  • Author(s): Fujihara K
  • Organizer: 27th Annual Meeting of the European Charcot Foundation. Baveno (Italy)
  • Int'l Joint Research / Invited
• [Presentation] (Closing Lecture) MOG-antibody-associated disease. From immunology to treatment (2019)
  • Author(s): Fujihara K
  • Organizer: Japanese Multiple Sclerosis Society International symposium. Tokyo (Japan),
  • Int'l Joint Research / Invited
• [Presentation] Neuromyelitis Optica, Clinical Aspects of Therapy (2019)
  • Author(s): Fujihara K
  • Organizer: 5th Middle-East and North African Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS), Decmber 6, Dubai (UAE)
  • Int'l Joint Research / Invited
• [Book] Pocket Drugs 2020 (2020)
  • Author(s): 藤原一男
  • Total Pages: 6
  • Publisher: 医学書院
  • ISBN: 978-4-260-03916-1