Development of detecting assay for anti-myelin oligodendrocyte glycoprotein antibody

• Project/Area Number: 20K07892
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: NAKASHIMA Ichiro 東北医科薬科大学, 医学部, 教授 (50333810)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 脱髄疾患 / 自己抗体 / 検査法 / MOG抗体関連疾患 / 多発性硬化症 / 視神経脊髄炎

Outline of Research at the Start

近年、中枢神経の炎症性脱髄疾患の中に抗ミエリンオリゴデンドロサイト糖蛋白（MOG）抗体が関与する病態が存在することが明らかになってきており、多発性硬化症や視神経脊髄炎とは異なる新たな疾患概念として確立しつつある。診断には抗MOG抗体の測定が必須であるが、現在の測定法は煩雑かつコストが高く、検査の普及を妨げており、保険適用に至っていない。本研究は診断マーカーとしての抗MOG抗体の新たな測定法の開発を目的とする。

Outline of Final Research Achievements

It is becoming clear that myelin oligodendrocyte glycoprotein (MOG) antibodies are involved in inflammatory demyelinating diseases of the central nervous system, and this is being established as a new disease concept distinct from multiple sclerosis and neuromyelitis optica. Measurement of MOG antibodies is essential for diagnosis, but the current measurement method is complicated and costly, preventing widespread use of the test, and has not yet been covered by insurance. In this study, we developed a new assay for MOG antibodies as a diagnostic marker and analyzed the clinical significance of MOG antibodies in relation to cytokines and other substances in serum and cerebrospinal fluid while conducting a nationwide epidemiological survey.

Academic Significance and Societal Importance of the Research Achievements

MOG抗体関連疾患はMOGADとよばれ、当科において初の全国疫学調査を実施した。これにより全国に1700人程度の患者が存在していることがあきらかになった。また、国際的なMOGADの診断基準が提唱され、今後独立した疾患概念として確立していく疾患である。一方でMOG抗体の測定は保険適用になっておらず、測定法のキット化が必要であり、感度および特異度の高い検査法の確立が求められている。今回の研究により開発を進めているMOG抗体測定法を今後キット化することにより、疾患の診断が容易になるため、臨床的な意義が大きい。

Research Products

• [Journal Article] Complement-dependent cytotoxicity of human autoantibodies against myelin oligodendrocyte glycoprotein (2023)
  • Author(s): Kohyama Kuniko、Nishida Hiroya、Kaneko Kimihiko、Misu Tatsuro、Nakashima Ichiro、Sakuma Hiroshi
  • Journal Title: Frontiers in Neuroscience Volume: 17 Pages: 1014071-1014071
  • DOI: 10.3389/fnins.2023.1014071
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiological and clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in a nationwide survey (2023)
  • Author(s): Nakamura Masashi、Ogawa Ryo、Fujimori Juichi、Uzawa Akiyuki、Sato Yasunori、Nagashima Kengo、Kuriyama Nagato、Kuwabara Satoshi、Nakashima Ichiro
  • Journal Title: Multiple Sclerosis Journal Volume: － Issue: 4-5 Pages: 530-539
  • DOI: 10.1177/13524585231156736
  • Peer Reviewed
• [Journal Article] White blood cell count profiles in anti-aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (2023)
  • Author(s): Akaishi Tetsuya、Misu Tatsuro、Fujihara Kazuo、Nakaya Kumi、Nakaya Naoki、Nakamura Tomohiro、Kogure Mana、Hatanaka Rieko、Itabashi Fumi、Kanno Ikumi、Kaneko Kimihiko、Takahashi Toshiyuki、Fujimori Juichi、Takai Yoshiki、Nishiyama Shuhei、Ishii Tadashi、Aoki Masashi、Nakashima Ichiro、Hozawa Atsushi
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 6481-6481
  • DOI: 10.1038/s41598-023-33827-3
  • Peer Reviewed / Open Access
• [Journal Article] Follow-up of retinal thickness and optic MRI after optic neuritis in anti-MOG antibody-associated disease and anti-AQP4 antibody-positive NMOSD (2022)
  • Author(s): Akaishi Tetsuya、Himori Noriko、Takeshita Takayuki、Misu Tatsuro、Takahashi Toshiyuki、Takai Yoshiki、Nishiyama Shuhei、Kaneko Kimihiko、Fujimori Juichi、Ishii Tadashi、Aoki Masashi、Fujihara Kazuo、Nakazawa Toru、Nakashima Ichiro
  • Journal Title: Journal of the Neurological Sciences Volume: 437 Pages: 120269-120269
  • DOI: 10.1016/j.jns.2022.120269
  • Peer Reviewed
• [Journal Article] GRP78 Antibodies Are Associated With Blood-Brain Barrier Breakdown in Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (2021)
  • Author(s): Shimizu F, Ogawa R, Mizukami Y, Watanabe K, Hara K, Kadono C, Takahashi T, Misu T, Takeshita Y, Sano Y, Fujisawa M, Maeda T, Nakashima I, Fujihara K, Kanda T.
  • Journal Title: Neurol Neuroimmunol Neuroinflamm Volume: 9 Issue: 1
  • DOI: 10.1212/nxi.0000000000001038
  • Peer Reviewed / Open Access
• [Journal Article] A nation-wide survey of Japanese pediatric MOG antibody-associated diseases (2021)
  • Author(s): Azumagawa Kohji、Nakashima Ichiro、Kaneko Kimihiko、Torisu Hiroyuki、Sakai Yasunari、Kira Ryutaro、Sakuma Hiroshi、Tanaka Keiko、Shigeri Yasushi、Tanaka Yoshie、Nakajima Hideto、Shimakawa Shuichi、Tamai Hiroshi
  • Journal Title: Brain and Development Volume: 43 Issue: 6 Pages: 705-713
  • DOI: 10.1016/j.braindev.2021.01.008
  • Peer Reviewed
• [Journal Article] Difference in the Source of Anti-AQP4-IgG and Anti-MOG-IgG Antibodies in CSF in Patients With Neuromyelitis Optica Spectrum Disorder. (2021)
  • Author(s): Akaishi T, Takahashi T, Misu T, Kaneko K, Takai Y, Nishiyama S, Ogawa R, Fujimori J, Ishii T, Aoki M, Fujihara K, Nakashima I.
  • Journal Title: Neurology. Volume: 97 Issue: 1
  • DOI: 10.1212/wnl.0000000000012175
  • Peer Reviewed / Open Access
• [Journal Article] Five-year visual outcomes after optic neuritis in anti-MOG antibody-associated disease. (2021)
  • Author(s): Akaishi T, Himori N, Takeshita T, Misu T, Takahashi T, Takai Y, Nishiyama S, Fujimori J, Ishii T, Aoki M, Fujihara K, Nakazawa T, Nakashima I.
  • Journal Title: Mult Scler Relat Disord Volume: 56 Pages: 103222-103222
  • DOI: 10.1016/j.msard.2021.103222
  • Peer Reviewed / Open Access
• [Journal Article] Myelin oligodendrocyte glycoprotein-IgG-positive, steroid-responsive combined central and peripheral demyelination with recurrent peripheral neuropathy. (2021)
  • Author(s): Nakamura T, Kaneko K, Watanabe G, Harashima S, Kawasaki E, Tsukita K, Takahashi T, Nakashima I, Misu T, Suzuki Y.
  • Journal Title: Neurol Sci Volume: 42 Issue: 3 Pages: 1135-1138
  • DOI: 10.1007/s10072-020-04822-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-NMDAR encephalitis may develop concurrently with anti-MOG antibody-associated bilateral medial frontal cerebral cortical encephalitis and relapse with elevated CSF IL-6 and CXCL13 (2021)
  • Author(s): Fujimori Juichi、Takahashi Toshiyuki、Kaneko Kimihiko、Atobe Yuri、Nakashima Ichiro
  • Journal Title: Multiple Sclerosis and Related Disorders Volume: 47 Pages: 102611-102611
  • DOI: 10.1016/j.msard.2020.102611
  • Peer Reviewed
• [Journal Article] Recent advances in the understanding of myelin oligodendrocyte glycoprotein antibody?associated disorders (2021)
  • Author(s): Nakashima Ichiro
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 12 Issue: 1 Pages: 4-4
  • DOI: 10.1111/cen3.12629
  • Peer Reviewed
• [Journal Article] Progression pattern of neurological disability with respect to clinical attacks in anti-MOG antibody-associated disorders (2021)
  • Author(s): Akaishi Tetsuya、Misu Tatsuro、Takahashi Toshiyuki、Takai Yoshiki、Nishiyama Shuhei、Fujimori Juichi、Ishii Tadashi、Aoki Masashi、Fujihara Kazuo、Nakashima Ichiro
  • Journal Title: Journal of Neuroimmunology Volume: 351 Pages: 577467-577467
  • DOI: 10.1016/j.jneuroim.2020.577467
  • Peer Reviewed / Open Access
• [Journal Article] Osmotic pressure of serum and cerebrospinal fluid in patients with suspected neurological conditions (2020)
  • Author(s): Akaishi Tetsuya、Takahashi Toshiyuki、Nakashima Ichiro、Abe Michiaki、Aoki Masashi、Ishii Tadashi
  • Journal Title: Neural Regeneration Research Volume: 15 Issue: 5 Pages: 944-944
  • DOI: 10.4103/1673-5374.268906
  • 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 Issue: 5 Pages: 1431-1446
  • DOI: 10.1093/brain/awaa102
  • Peer Reviewed / Open Access / 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 Issue: 6 Pages: 605-611
  • DOI: 10.1136/jnnp-2019-322286
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Steroid-responsive recurrent tumefactive demyelination with multiple petechial hemorrhages along non-displaced medullary veins (2020)
  • Author(s): Tsuboi Takashi、Harada Yumiko、Suzuki Masashi、Ando Takashi、Atsuta Naoki、Ohka Fumiharu、Takeuchi Kazuhito、Taoka Toshiaki、Ohba Shigeo、Nakaguro Masato、Abe Masato、Nakashima Ichiro、Yoshida Mari、Katsuno Masahisa
  • Journal Title: Clinical Neurology and Neurosurgery Volume: 193 Pages: 105764-105764
  • DOI: 10.1016/j.clineuro.2020.105764
  • Peer Reviewed
• [Journal Article] Unilateral chronic pulsatile headache as the single manifestation of anti-MOG antibody-associated unilateral cerebral cortical encephalitis (2020)
  • Author(s): Fujimori Juichi、Ogawa Ryo、Murata Takaki、Jin Kazutaka、Yazawa Yukako、Nakashima Ichiro
  • Journal Title: Journal of Neuroimmunology Volume: 346 Pages: 577322-577322
  • DOI: 10.1016/j.jneuroim.2020.577322
  • Peer Reviewed
• [Journal Article] Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide (2020)
  • Author(s): Hor Jyh Yung、Asgari Nasrin、Nakashima Ichiro、Broadley Simon A.、Leite M. Isabel、Kissani Najib、Jacob Anu、Marignier Romain、Weinshenker Brian G.、Paul Friedemann、Pittock Sean J.、Palace Jacqueline、Wingerchuk Dean M.、Behne Jacinta M.、Yeaman Michael R.、Fujihara Kazuo
  • Journal Title: Frontiers in Neurology Volume: 11 Pages: 501-13
  • DOI: 10.3389/fneur.2020.00501
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients. (2020)
  • Author(s): Whittam DH, Cobo-Calvo A, Lopez-Chiriboga AS, Pardo S, E, Ciron J, Deschamps R, Biotti D, Rostasy K, Neuteboom R, HemingwaGornall M, Cicconi S, Brandt A, Berek K, Berger T, Jelcic I, Gombolay G, Oliveira LM, Callegaro D, Kaneko K, Misu T, et al.
  • Journal Title: Mult Scler Relat Disord Volume: 44 Pages: 102251-102251
  • DOI: 10.1016/j.msard.2020.102251
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differences in Clinical Features of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis in White and Asian Race (2020)
  • Author(s): Padungkiatsagul Tanyatuth、Chen John J.、Jindahra Panitha、Akaishi Tetsuya、Takahashi Toshiyuki、Nakashima Ichiro、Takeshita Takayuki、Moss Heather E.
  • Journal Title: American Journal of Ophthalmology Volume: 219 Pages: 332-340
  • DOI: 10.1016/j.ajo.2020.07.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Treatment of MOG antibody associated disorders: results of an international survey (2020)
  • Author(s): Whittam Daniel H、Nakashima Ichiro、Fujihara Kazuo、Sato Douglas Kazutoshi、et al.
  • Journal Title: Journal of Neurology Volume: 267 Issue: 12 Pages: 3565-3577
  • DOI: 10.1007/s00415-020-10026-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Seasonal variation of onset in patients with anti-aquaporin-4 antibodies and anti-myelin oligodendrocyte glycoprotein antibody (2020)
  • Author(s): Akaishi Tetsuya、Fujimori Juichi、Takahashi Toshiyuki、Misu Tatsuro、Takai Yoshiki、Nishiyama Shuhei、Kaneko Kimihiko、Ogawa Ryo、Abe Michiaki、Ishii Tadashi、Aoki Masashi、Fujihara Kazuo、Nakashima Ichiro
  • Journal Title: Journal of Neuroimmunology Volume: 349 Pages: 577431-577431
  • DOI: 10.1016/j.jneuroim.2020.577431
  • Peer Reviewed
• [Journal Article] Clinical and Radiological Features of Adult Onset Bilateral Medial Frontal Cerebral Cortical Encephalitis With Anti-myelin Oligodendrocyte Glycoprotein Antibody (2020)
  • Author(s): Fujimori Juichi、Nakamura Masashi、Yagihashi Takahito、Nakashima Ichiro
  • Journal Title: Frontiers in Neurology Volume: 11 Pages: 1-5
  • DOI: 10.3389/fneur.2020.600169
  • Peer Reviewed / Open Access