Significance of anti-neutral glycolipid antibody in encephalomyeloradiculoneuropathy(EMRN)

• Project/Area Number: 26461299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Fujita Health University
• Principal Investigator: Shima Sayuri 藤田保健衛生大学, 医学部, 講師 (50725984)
• Co-Investigator(Kenkyū-buntansha): 武藤 多津郎 藤田保健衛生大学, 医学部, 教授 (60190857)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Lipid rafts / 脳脊髄根末梢神経炎 / neutral glycolipid / 自己免疫 / 中枢・末梢脱髄連合症（CCPD） / lipid rafts / neutral ｇlycolipid / 中枢・末梢脱髄症（CCPD）

Outline of Final Research Achievements

Encephalomyeloradiculoneuroapthy (EMRN) is a devastating disorder involved in central and　peripheral nervous systems. In 2014, we found autoantibodies against neutral glycolipids in EMRN were present and their titers well correlated to the status of clinical conditions. In this study, we explored biological activities of these autoantibodies and the molecular mechanisms how these autoantibodies are produced. The data disclosed the following facts; 1) all EMRN cases exhibit antibodies against neutral glycolipids, mainly to lactosylceramide in their sera and/or CSF; 2) clinical pictures of EMRN seemed rather uniform, but the reactivities against immune modulatory therapies showed varieties; 3) anti-neutral glycolipids antibodies are sensitive to fatty acid chain length of respective neutral glycolipids; 4) CSF samples from EMRN cases exhibited significant abnormal compositions of glycolipids compared with normal controls based upon the LC/MS/MS highly sensitive assay method.

Research Products

• [Journal Article] Usefulness of combining 123I-FP-CIT-SPECT striatal asymmetry index and cardiac 123I-metaiodobenzylguanidine scintigraphy examinations for diagnosis of parkinsonisms. (2017)
  • Author(s): Niimi Y, Ito S, Murate K, Hirota S, Hikichi C, Ishikawa T, Maeda T, Nagao R, Shima S, Mizutani Y, Ueda A, Mutoh T.
  • Journal Title: J Neurol Sci Volume: 377 Pages: 174-178
  • DOI: 10.1016/j.jns.2017.04.026
  • Peer Reviewed
• [Journal Article] MR neurography for the evaluation of CIDP. (2017)
  • Author(s): Ishikawa T, Asakura K, Mizutani Y, Ueda A, Murate KI, Hikichi C, Shima S, Kizawa M, Komori M, Murayama K, Toyama H, Ito S, Mutoh T.
  • Journal Title: Muscle Nerve. Volume: 55 Issue: 4 Pages: 483-489
  • DOI: 10.1002/mus.25368
  • Peer Reviewed / Open Access
• [Journal Article] Current Understanding of Immunopathogenesis of Parkinson’s Disease. (2016)
  • Author(s): Mutoh T
  • Journal Title: Austin J Clin Neurol Volume: 3 Pages: 1097-1098
  • Peer Reviewed / Open Access
• [Journal Article] Differentiation of cancer from atrial fibrillation in patients with acute multifocal stroke. (2016)
  • Author(s): Ito S, Ueda A, Murate K, Hirota S, Fukui T, Ishikawa T, Shima S, Hikichi C, Mizutani Y, Kizawa M, Asakura K, Mutoh T
  • Journal Title: J Neurol Sci Volume: 15 Pages: 344-348
  • DOI: 10.1016/j.jns.2016.07.054
  • Peer Reviewed / Open Access
• [Journal Article] Muscle MRI of the Upper Extremity in the Myotonic Dystrophy Type 1 (2016)
  • Author(s): K. Hayashi, T. Hamano, Y. Kawamura, H. Kimura, A. Matsunaga, M. Ikawa, O. Yamamura, T. Mutoh, I. Higuchi, M. Kuriyama, Y. Nakamoto
  • Journal Title: Eur Neurol Volume: 76 Issue: 1-2 Pages: 87-94
  • DOI: 10.1159/000448328
  • Peer Reviewed / Open Access
• [Journal Article] Hypertrophic Cardiomyopathy Accompanied by Spinocerebellar Atrophy With a Novel Mutation in Troponin I Gene (2016)
  • Author(s): Kawai H, Morimoto S, Takakuwa Y, Ueda A, Inada K, Sarai M, Arimura T, Mutoh T, Kimura A, Ozaki Y
  • Journal Title: International Heart Journal Volume: 57 Issue: 4 Pages: 507-510
  • DOI: 10.1536/ihj.15-444
  • NAID: 130006895905
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Relapsing polychondritis-associated limbic encephalitis preceding the emergence of systemic inflammation (2016)
  • Author(s): Miho Kawabe,*, Rintaro Tachi, Takuto Hideyama, Masato Yagi, Yukiko Kishida, Risa Maekawa, Sayuri Shima, Tatsuro Mutoh and Yasushi Shiio
  • Journal Title: Neurology and Clinical Neuroscience Volume: online Issue: 4 Pages: 0-0
  • DOI: 10.1111/ncn3.12060
  • Peer Reviewed / Open Access
• [Journal Article] Phase II Trial of Intravenous Low-Dose Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke (2016)
  • Author(s): Mizuma A, Yamashita T, Kono S, Nakayama T, Baba Y, Itoh S, Asakura K, Niimi Y, Asahi T, Kanemaru K, Mutoh T, Kuroda S, Kinouchi H, Abe K, Takizawa S.
  • Journal Title: J Stroke Cerebrovasc Dis Volume: Epub ahead of print Issue: 6 Pages: 0-0
  • DOI: 10.1016/j.jstrokecerebrovasdis.2016.01.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Case of limbic encephalitis with anti-neutral glycosphingolipid antibodies (2016)
  • Author(s): Yuko Takeuchi, Miki Ueda, Jun Ochiai, Chiyuki Mabuchi, Sayuri Shima and Tatsuro Mutoh
  • Journal Title: Neurology and Clinical Neuroscience Volume: 4 Issue: 2 Pages: 70-72
  • DOI: 10.1111/ncn3.12037
  • Peer Reviewed / Open Access
• [Journal Article] Depressive state as an initial symptom for subdural abscess (2016)
  • Author(s): Fukui T, Ueda A, Murate K-I, Hikichi C, Ito S, Asakura K, Mutoh T
  • Journal Title: Neurol Clin Neurosci Volume: 4(1) Issue: 1 Pages: 31-3
  • DOI: 10.1111/ncn3.12029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Items: 7 Select item 26671120 1. Retrospective analysis of parkinsonian patients exhibiting normal (123)I-MIBG cardiac uptake. (2015)
  • Author(s): Mizutani Y, Ito S, Murate K, Hirota S, Fukui T, Hikichi C, Ishikawa T, Shima S, Ueda A, Kizawa M, Asakura K, Mutoh T
  • Journal Title: J Neurol Sci Volume: 359 Issue: 1-2 Pages: 236-240
  • DOI: 10.1016/j.jns.2015.10.059
  • Peer Reviewed / Open Access
• [Journal Article] Voriconazole-responsive Disseminated Nodular Lesions on Spinal MRI (2015)
  • Author(s): Hirota S, Ito S, Fukui T, Murate K, Shima S, Kizawa M, Ueda A, Asakura K, Mutoh T.
  • Journal Title: Internal Medicine Volume: 54 Issue: 2 Pages: 215-218
  • DOI: 10.2169/internalmedicine.54.3148
  • NAID: 130004903008
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Hypertrophic pachymeningitis and encephalitis in a patient with relapsing polychondritis (2015)
  • Author(s): Nakamura K, Sugaya K, Nakata Y, Shima S, Mutoh T, Nakano I.
  • Journal Title: Neurology and Clinical Neuroscience Volume: 3 Issue: 1 Pages: 42-3
  • DOI: 10.1111/ncn3.130
  • Peer Reviewed / Open Access
• [Journal Article] Targeting of aquaporin 4 into lipid rafts and its biological significance. (2014)
  • Author(s): Asakura K, Ueda A, Shima S, Ishikawa T, Hikichi C, Hirota S, Fukui T, Ito S, Mutoh T.
  • Journal Title: Ｂｒａｉｎ Ｒｅｓｅａｒｃｈ Volume: 1583 Pages: 237-244
  • DOI: 10.1016/j.brainres.2014.08.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 亜急性軸索型ニューロパチー症例に認められた抗Trk抗体の意義 (2014)
  • Author(s): 廣田政古、植田晃広、稲熊容子、島さゆり、恵美宣彦、武藤多津郎
  • Journal Title: 末梢神経 Volume: 25 Pages: 100-106
  • Peer Reviewed / Open Access
• [Presentation] CIDP患者末梢神経組織の画像化と定量の試み (2017)
  • Author(s): 武藤多津郎、石川等真、植田晃広、島さゆり、村手健一郎、伊藤信二.
  • Organizer: 平成28年度免疫性ニューロパチー班班会議
  • Place of Presentation: 都市センターホテル
• [Presentation] Clioquinolの神経系細胞に及ぼす影響の解明 (2017)
  • Author(s): 武藤多津郎、村手健一郎、新美芳樹、水谷泰彰、島さゆり、植田晃広、伊藤信二.
  • Organizer: 平成28年度スモンに関する調査研究班班会議
  • Place of Presentation: フクラシア東京ステーション
• [Presentation] 視神経炎を合併した抗NMDA受容体（NMDAR）脳炎の１例, (2017)
  • Author(s): 廣田政古、伊藤信二、植田晃広、長尾龍之介、前田利樹、村手健一郎、引地智加、石川等真、島さゆり、新美芳樹、武藤多津郎.
  • Organizer: 第147回神経学会地方会,
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Clinical and Biochemical pictures of anti-neutral glycolipids antibody-positive central and peripheral nervous system-involving disorders. (2016)
  • Author(s): Tatsuro Mutoh, Sayuri Shima, Akihiro Ueda, Kunihiko Asakura, Shinji Ito
  • Organizer: American Academy of Neurology
  • Place of Presentation: Vancouver Convention Centre / Vancouver, BC, Canada.
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] Clinical and Biochemical pictures of anti-neutral glycolipids antibody-positive central and peripheral nervous system-involving disorders, (2016)
  • Author(s): Mutoh T, Shima S, Ueda A, Asakura K, Ito S
  • Organizer: AAN
  • Place of Presentation: アメリカ、バンクーバー
  • Int'l Joint Research
• [Presentation] 自験16例から分析した脳脊髄根末梢神経炎（EMRN）の臨床像と抗体活性, (2016)
  • Author(s): 島さゆり、植田晃広、水谷泰彰、村手健一郎、廣田政古、引地智加、石川等真、新美芳樹、木澤真努香、伊藤信二、武藤多津郎.
  • Organizer: 第57回 日本神経学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] CIDP患者における末梢神経のvolume解析 (2016)
  • Author(s): 石川等真、水谷泰彰、 引地智加、島さゆり、植田晃広、木澤真努香、伊藤信二、武藤多津郎
  • Organizer: 第57回 日本神経学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Clioquinol induces apoptosis in PC12 cells via caspase 9 and 3 Activation (2016)
  • Author(s): 朝倉邦彦、石川等真、島さゆり、植田晃広、伊藤信二、武藤多津郎.
  • Organizer: 第57回 日本神経学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] The significance of serial D-dimer measurements on Trousseau's syndrome (2016)
  • Author(s): 伊藤信二、村手健一郎、廣田政古、引地智加、石川等真、島さゆり、 水谷泰彰、植田晃広、木澤真努香、武藤多津郎
  • Organizer: 第57回 日本神経学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 言語障害で発症し、脳内にMRI異常信号が多発した51歳女性例 (2016)
  • Author(s): 村手健一郎、前田利樹、長尾龍之介、廣田政古、引地智加、石川等真、島さゆり、新美芳樹、植田晃広、伊藤信二、武藤多津郎
  • Organizer: 第145回 日本神経学会東海北陸地方会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 抗GM1抗体の中性スフィンゴミエリナーゼに及ぼす影響の解明, (2016)
  • Author(s): 植田晃広、村手健一郎、廣田政古、引地智加、石川等真、島さゆり、新美芳樹、伊藤信二、武藤多津郎.
  • Organizer: 第28回 神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール
• [Presentation] CIDP患者における末梢神経のMRI neurographyを用いた定量的解析の試み (2016)
  • Author(s): 石川等真、新美芳樹、植田晃広、村手健一郎、廣田政古、引地智加、島さゆり、伊藤信二、武藤多津郎
  • Organizer: 第48回 藤田医学会
  • Place of Presentation: 藤田保健衛生大学
• [Presentation] 反復する一過性複視を呈し神経梅毒と考えられた1例 (2016)
  • Author(s): 石川等真、伊藤信二、長尾龍之介、前田利樹、村手健一郎、廣田政古、引地智加、島さゆり、新美芳樹、植田晃広、武藤多津郎.
  • Organizer: 第21回 日本神経感染症学会総会・学術大会
  • Place of Presentation: 金沢東急ホテル
• [Presentation] 抗Th/To抗体，抗SRP抗体陽性壊死性筋炎の1例 (2016)
  • Author(s): ,引地智加、伊藤信二、長尾龍之介、前田利樹、村手健一郎、廣田政古、石川等真、島さゆり、新美芳樹、植田晃広、武藤多津郎.
  • Organizer: 第146回 日本神経学会東海北陸地方会,
  • Place of Presentation: 石川県地場産業振興センター
• [Presentation] 妊娠中に発症し免疫治療と帝王切開により健康な児を得て母体も回復し得たNMDAR脳炎の１症例 (2016)
  • Author(s): 植田晃広、長尾龍之介、前田利樹、村手健一郎、廣田政古、引地智加、石川等真、新美芳樹、伊藤信二、武藤多津郎.
  • Organizer: 第34回 日本神経治療学会総会,
  • Place of Presentation: 米子コンベンションセンター
• [Presentation] 脳脊髄根末梢神経炎(EMRN)の臨床像と治療反応性 (2015)
  • Author(s): 島 さゆり 武藤多津郎
  • Organizer: 日本神経治療学会・総会
  • Place of Presentation: 名古屋国際会議場/愛知県
  • Year and Date: 2015-11-27
• [Presentation] 脳脊髄根末梢神経炎（EMRN: Encephalomyeloradiculoneuropathy）に認められる抗中性糖脂質抗体の抗原特異性 (2015)
  • Author(s): 島 さゆり 武藤多津郎
  • Organizer: 日本神経免疫学会
  • Place of Presentation: 長良川国際会議場/岐阜県
  • Year and Date: 2015-09-16
• [Presentation] 東海北陸地方会 脳炎症状が先行し、速やかに回復した抗中性糖脂質抗体陽性EMRNの一例 (2015)
  • Author(s): 水谷 泰彰 島 さゆり 武藤多津郎
  • Organizer: 日本神経学会 東海北陸地方会
  • Place of Presentation: 名古屋国際会議場/愛知県
  • Year and Date: 2015-06-25
• [Presentation] 抗中性糖脂質抗体が陽性であったEMRNの一例 (2014)
  • Author(s): 島さゆり
  • Organizer: 日本神経学会東海北陸地方会
  • Place of Presentation: 福井県国際交流会館/福井県
  • Year and Date: 2014-11-01
• [Presentation] 脳脊髄根末梢神経炎(EMRN）患者血清中に見出された新規抗中性糖脂質抗体 (2014)
  • Author(s): 島 さゆり
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場/福岡県
  • Year and Date: 2014-05-21 – 2014-05-25
• [Presentation] New Autoantibodies Against Neutral Glycolipids In Encephalomyeloradiculoneuropathy. (2014)
  • Author(s): Mutoh T
  • Organizer: The 66thAmerican Academy of Neurology Annual Meeting
  • Place of Presentation: Philadelphia
  • Year and Date: 2014-04-26 – 2014-05-03
• [Remarks] 藤田保健衛生大学 教員の学位及び業績（医学部）
  • URL: http://www.fujita-hu.ac.jp/open_info/08/med.html
• [Remarks] 藤田保健衛生大学 医学部 脳神経内科学 教室
  • URL: http://www.fujita-hu.ac.jp/~sinkei