Investigation of the autoantibodies against complex antigens formed by two lipid molecules in neuroimmunological diseases

• Project/Area Number: 18H02745
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kindai University
• Principal Investigator: KUSUNOKI Susumu 近畿大学, 医学部, 客員教授 (90195438)
• Co-Investigator(Kenkyū-buntansha): 桑原 基 近畿大学, 医学部, 講師 (40460860) ; 宮本 勝一 近畿大学, 医学部, 准教授 (50388526)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 免疫性神経疾患 / 自己抗体 / 糖脂質 / 脂質複合体 / ガングリオシド

Outline of Final Research Achievements

Autoantibodies in neuroimmunological diseases against complex antigens formed by glycolipids and phospholipids or cholesterol were investigated. IgM antibodies to complex antigens including such myelin antigens as Gal-C and sulfatide were frequently detected in chronic inflammatory demyelinating polyneuropathy. Those antibodies may be involved in the pathogenetic mechanism of demyelination. In multifocal motor neuropathy, the positive rate of IgM anti-GM1 antibodies was increased when phosphatidic acid was added to the GM1 antigen. IgG anti-GD1a antibodies were found to be associated with Guillain-Barre syndrome with poor prognosis. Patients with Bickerstaff brainstem encephalitis having GQ1b-related antibodies showed relatively uniform clinical features.

Academic Significance and Societal Importance of the Research Achievements

慢性炎症性脱髄性多発ニューロパチーや多巣性運動ニューロパチーなど、自己免疫によっておこる末梢神経障害で、病気を引き起こす原因となる自己抗体の候補が見いだされた。
回復の遅いギラン・バレー症候群に関連する因子が見いだされ、予後予測に使用できる可能性が示された。ビッカースタッフ脳幹脳炎におけるGQ1b関連抗体の臨床的意義が示された。

Research Products

• [Int'l Joint Research] University of Milan(イタリア)
• [Int'l Joint Research] University of Milan(イタリア)
• [Journal Article] Antiglycolipid antibodies in Guillain-Barre and Fisher syndromes: discovery, current status and future perspective (2021)
  • Author(s): Kusunoki Susumu、Willison Hugh J、Jacobs Bart C
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 92 Issue: 3 Pages: 311-318
  • DOI: 10.1136/jnnp-2020-325053
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum IgG anti-GD1a antibody and mEGOS predict outcome in Guillain-Barre syndrome (2020)
  • Author(s): Yamagishi Yuko、Kuwahara Motoi、Suzuki Hidekazu、Sonoo Masahiro、Kuwabara Satoshi、Yokota Takanori、Nomura Kyoichi、Chiba Atsuro、Kaji Ryuji、Kanda Takashi、Kaida Ken-ichi、Mutoh Tatsuro、Yamasaki Ryo、Takashima Hiroshi、Matsui Makoto、Nishiyama Kazutoshi、Sobue Gen、Kusunoki Susumu
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 91 Issue: 12 Pages: 1339-1342
  • DOI: 10.1136/jnnp-2020-323960
  • Peer Reviewed
• [Journal Article] Bickerstaff brainstem encephalitis with or without anti-GQ1b antibody (2020)
  • Author(s): Yoshikawa Keisuke、Kuwahara Motoi、Morikawa Miyuki、Kusunoki Susumu
  • Journal Title: Neurology - Neuroimmunology Neuroinflammation Volume: 7 Issue: 6
  • DOI: 10.1212/nxi.0000000000000889
  • Peer Reviewed / Open Access
• [Journal Article] Association of variability in antibody binding affinity with a clinical course of anti-MAG neuropathy. (2020)
  • Author(s): Matsui T, Hamada Y, Kuwahara M, Morise J, Oka S, Kaida K, Kusunoki S.
  • Journal Title: J. Neuroimmunol. Volume: 339 Pages: 577127-577127
  • DOI: 10.1016/j.jneuroim.2019.577127
  • Peer Reviewed
• [Journal Article] Complement deposition and macrophage-induced demyelination in CIDP with anti-LM1 antibodies (2020)
  • Author(s): Koike Haruki、Ikeda Shohei、Fukami Yuki、Nishi Ryoji、Kawagashira Yuichi、Iijima Masahiro、Nakamura Tomohiko、Kuwahara Motoi、Kusunoki Susumu、Katsuno Masahisa、Sobue Gen
  • Journal Title: Journal of the Neurological Sciences Volume: 408 Pages: 116509-116509
  • DOI: 10.1016/j.jns.2019.116509
  • Peer Reviewed
• [Journal Article] Guillain-Barre syndrome and related diseases after influenza virus infection (2019)
  • Author(s): Yamana Masaki、Kuwahara Motoi、Fukumoto Yuta、Yoshikawa Keisuke、Takada Kazuo、Kusunoki Susumu
  • Journal Title: Neurology - Neuroimmunology Neuroinflammation Volume: 6 Issue: 4
  • DOI: 10.1212/nxi.0000000000000575
  • Peer Reviewed / Open Access
• [Journal Article] Multifocal nodular hypertrophy of trigeminal nerve in multifocal acquired demyelinating sensory and motor neuropathy (2019)
  • Author(s): Kuwahara Motoi、Numoto Isao、Kusunoki Susumu
  • Journal Title: Neurology - Neuroimmunology Neuroinflammation Volume: 6 Issue: 3
  • DOI: 10.1212/nxi.0000000000000553
  • Peer Reviewed / Open Access
• [Journal Article] Current treatment practice of Guillain-Barre syndrome (2019)
  • Author(s): Verboon Christine、Doets Alex Y.、Galassi Giuliana、Davidson Amy、Waheed Waqar、Pereon Yann、Shahrizaila Nortina、Kusunoki Susumu、Lehmann Helmar C.、Harbo Thomas、Monges Soledad、Van den Bergh Peter、Willison Hugh J.、Cornblath David R.、Jacobs Bart C.、on behalf of the IGOS Consortium
  • Journal Title: Neurology Volume: 93 Issue: 1
  • DOI: 10.1212/wnl.0000000000007719
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Second IVIg course in Guillain-Barre syndrome with poor prognosis: the non-randomised ISID study (2019)
  • Author(s): Verboon C, van den Berg B, Cornblath DR, Venema E, Gorson KC, Lunn MP, Lingsma H, Van den Bergh P, Harbo T, Bateman K, Pereon Y, Sindrup SH, Kusunoki S, Miller J, Islam Z, Hartung HP, Chavada G, Jacobs BC, Hughes RAC, van Doorn PA; IGOS Consortium.
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 91 Issue: 2 Pages: 113-121
  • DOI: 10.1136/jnnp-2019-321496
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diagnosis and management of Guillain-Barre syndrome in ten steps (2019)
  • Author(s): Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, van Doorn PA, Dourado ME, Hughes RAC, Islam B, Kusunoki S, Pardo CA, Reisin R, Sejvar JJ, Shahrizaila N, Soares C, Umapathi T, Wang Y, Yiu EM, Willison HJ, Jacobs BC.
  • Journal Title: Nature Reviews Neurology Volume: 15 Issue: 11 Pages: 671-683
  • DOI: 10.1038/s41582-019-0250-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Varied antibody reactivities and clinical relevance in anti-GQ1b antibody?related diseases (2018)
  • Author(s): Yoshikawa Keisuke、Kuwahara Motoi、Morikawa Miyuki、Fukumoto Yuta、Yamana Masaki、Yamagishi Yuko、Kusunoki Susumu
  • Journal Title: Neurology - Neuroimmunology Neuroinflammation Volume: 5 Issue: 6
  • DOI: 10.1212/nxi.0000000000000501
  • Peer Reviewed / Open Access
• [Journal Article] Regional variation of Guillain-Barr? syndrome (2018)
  • Author(s): Doets Alex Y、Verboon Christine、Susumu Kusunoki（44人中28番目）、Bart Jacobs、他40名
  • Journal Title: Brain Volume: 141 Issue: 10 Pages: 2866-2877
  • DOI: 10.1093/brain/awy232
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 4-Aminopyridine ameliorates relapsing remitting experimental autoimmune encephalomyelitis in SJL/J mice (2018)
  • Author(s): Moriguchi Kota、Miyamoto Katsuichi、Fukumoto Yuta、Kusunoki Susumu
  • Journal Title: Journal of Neuroimmunology Volume: 323 Pages: 131-135
  • DOI: 10.1016/j.jneuroim.2018.08.007
  • Peer Reviewed
• [Journal Article] Safety and efficacy of eculizumab in Guillain-Barre syndrome: a multicentre, double-blind, randomised phase 2 trial (2018)
  • Author(s): Misawa S, Kuwabara S, Sato Y, Yamaguchi N, Nagashima K, Katayama K, Sekiguchi Y, et al
  • Journal Title: Lancet neuro Volume: 17 Issue: 6 Pages: 519-529
  • DOI: 10.1016/s1474-4422(18)30114-5
  • Peer Reviewed
• [Presentation] ガングリオシド抗体陽性ニューロパチー (2020)
  • Author(s): 桑原基
  • Organizer: 第38回日本神経治療学会学術集会
  • Invited
• [Presentation] CIDPにおける臨床病型と自己抗体 (2020)
  • Author(s): 桑原基
  • Organizer: 第61回日本神経学会学術大会
  • Invited
• [Presentation] 免疫性ニューロパチー抗糖脂質抗体；これまでとこれから (2019)
  • Author(s): 楠 進
  • Organizer: 第60回日本神経学会学術大会
  • Invited
• [Presentation] 抗GQ1b関連抗体陽性Bickerstaff脳幹脳炎の臨床的特徴 (2019)
  • Author(s): 吉川恵輔、桑原基、森川みゆき、楠 進
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] Guillain-Barre syndrome and related diseases after influenza virus infection (2019)
  • Author(s): Yamana M, Kuwahara M, Kusunoki S
  • Organizer: PNS Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Clinical subtypes and anti-glycolipid antibodies in chronic inflammatory demyelinating polyneuropathy (2019)
  • Author(s): Kuwahara M, Matsui T,Yoshikawa K, Yamana M,Fukumoto Y, Kaida K, Kusunoki S
  • Organizer: PNS Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Association between anti-ganglioside antibodies and prognostic markers in Guillain-Barre syndorome (2019)
  • Author(s): Yamagishi Y, Kuwahara M, Sonoo M, Kuwabara S, Yokota T, Nomura K, Chiba A, Kaji R, Kanda T, Kaida K, Ikeda S, Mutoh T, Yamasaki R, Takashima H, Matsui M, Nishiyama K, Sobue G, Kusunoki S
  • Organizer: PNS Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] Different clinical findings between anti-GQ1b antibody-positive and -negative Bickerstaff Brainstem Encephalitis (2019)
  • Author(s): Yoshikawa K, Morikawa M, Kuwahara M, Kusunoki S
  • Organizer: PNS Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] 慢性炎症性脱髄性多発根ニューロパチーにおける臨床病型と自己抗体 (2019)
  • Author(s): 桑原 基、松井太郎、吉川恵輔、山名正樹、福本雄太、海田賢一、楠 進
  • Organizer: 第31回日本神経免疫学会学術集会
• [Presentation] Autoimmune neuropathies associated with anti-glycolipid antibodies. (2018)
  • Author(s): Kusunoki S.
  • Organizer: 16th Asian Oceanian Congress of Neurology
  • Int'l Joint Research / Invited
• [Presentation] Variability of the binding specificity of IgM M-proteins in anti-MAG neuropathy; possible clinical relevance. (2018)
  • Author(s): Kusunoki S, Matsui T, Hamada Y, Kuwahara M, Morise J, Oka S.
  • Organizer: 143rd Annual Meeting of the American Neurological Association
  • Int'l Joint Research
• [Presentation] Autoantibodies in chronic autoimmune neuropathies. (2018)
  • Author(s): Kusunoki S.
  • Organizer: International Symposium of Peripheral Neuropathy Research Center
  • Int'l Joint Research / Invited
• [Presentation] Autoantibodies and treatments in autoimmune neuropathies. (2018)
  • Author(s): Kusunoki S
  • Organizer: 14th ISNI Congress
  • Int'l Joint Research / Invited
• [Presentation] Differences of antibody reactivities against glycolipid complexes among GBS, MFS and BBE. (2018)
  • Author(s): Yoshikawa K, Morikawa M, Kuwahara M, Kusunoki S.
  • Organizer: 59th Annual Meeting of the Japanese Society of Neurology, Sapporo
• [Presentation] Bickerstaff Brainstem Encephalitis. (2018)
  • Author(s): Kusunoki S
  • Organizer: 59th Annual Meeting of the Japanese Society of Neurology
  • Invited
• [Presentation] 免疫性末梢神経障害の病態と治療 (2018)
  • Author(s): 楠 進
  • Organizer: 日本内科学会生涯教育講演会Aセッション
  • Invited