Analysis of target antigens and pathogenetic mechanisms of neuroimmunological diseases using glycoarray

• Project/Area Number: 15H04845
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kindai University
• Principal Investigator: KUSUNOKI Susumu 近畿大学, 医学部, 教授 (90195438)
• Co-Investigator(Kenkyū-buntansha): 桑原 基 近畿大学, 医学部, 講師 (40460860) ; 西郷 和真 近畿大学, 理工学部, 准教授 (50319688) ; 宮本 勝一 近畿大学, 医学部, 准教授 (50388526)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥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 / ガングリオシド / 末梢神経障害 / 脳神経疾患 / 脳脊髄炎 / ギラン・バレー症候群 / 糖鎖 / 脳・神経 / 神経科学 / 免疫学

Outline of Final Research Achievements

Serum antibodies to glycolipids and glycolipid complexes in patients with neuroimmunological diseases were investigated comprehensively using glycoarray. Antibody activities to glycolipid complexes containing sulfatide in Guillain-Barré syndrome (GBS) and to those containing GalNAc-GD1a in multifocal motor neuropathy (MMN) were newly found by the present study. It was suggested that those antibodies are involved in the pathogenetic mechanisms of GBS and MMN. Among the patients with anti-GQ1b antibody-associated diseases, antibodies to glycolipid complexes containing GD1b were frequently present in GBS. Patients with such antibodies were frequently affected with severe GBS. Clinical features of neuroimmunological diseases with anti-Gal-C antibodies and those of neuropathy with anti-neurofascin 155 antibodies were revealed.

Research Products

• [Journal Article] Mechanism and spectrum of anti-glycolipid antibody-mediated chronic inflammatory demyelinating polyneuropathy (2018)
  • Author(s): Kuwahara Motoi、Kusunoki Susumu
  • Journal Title: Clin Exp Neuroimmunol Volume: 9 Issue: 1 Pages: 65-74
  • DOI: 10.1111/cen3.12452
  • Peer Reviewed
• [Journal Article] ELectron microscopic abnormality and therapeutic efficacy in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin155 immunoglobulin G4 antibody (2017)
  • Author(s): Kuwahara Motoi、Suzuki Hidekazu、Oka Nobuyuki、Ogata Hidenori、Yanagimoto Satoshi、Sadakane Shuji、Fukumoto Yuta、Yamana Masaki、Yuhara Yoshiko、Yoshikawa Keisuke、Morikawa Miyuki、Kawai Shigeru、Okazaki Masahiro、Tsujimoto Toru、Kira Jun-Ichi、Kusunoki Susumu
  • Journal Title: Muscle Nerve Volume: 57 Issue: 3 Pages: 498-502
  • DOI: 10.1002/mus.25757
  • Peer Reviewed
• [Journal Article] International Guillain-Barre Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barre syndrome (2017)
  • Author(s): Jacobs Bart C.、van den Berg Bianca、Verboon Christine、Chavada Govindsinh、Cornblath David R.、Gorson Kenneth C.、Harbo Thomas、Hartung Hans-Peter、Hughes Richard A. C.、Kusunoki Susumu、van Doorn Pieter A.、Willison Hugh J.、the IGOS Consortium
  • Journal Title: J Peripher Nerv Syst Volume: 22 Issue: 2 Pages: 68-76
  • DOI: 10.1111/jns.12209
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Markers for Guillain-Barr? syndrome with poor prognosis: a multi-center study (2017)
  • Author(s): Yamagishi Yuko、Suzuki Hidekazu、Sonoo Masahiro、Kuwabara Satoshi、Yokota Takanori、Nomura Kyoichi、Chiba Atsuro、Kaji Ryuji、Kanda Takashi、Kaida Kenichi、Ikeda Shu-ichi、Mutoh Tatsuro、Yamasaki Ryo、Takashima Hiroshi、Matsui Makoto、Nishiyama Kazutoshi、Sobue Gen、Kusunoki Susumu
  • Journal Title: Journal of the Peripheral Nervous System Volume: 22 Issue: 4 Pages: 433-439
  • DOI: 10.1111/jns.12234
  • Peer Reviewed / Open Access
• [Journal Article] Acute demyelinating polyneuropathy induced by nivolumab (2017)
  • Author(s): Fukumoto Yuta、Kuwahara Motoi、Kawai Shigeru、Nakahama Kenji、Kusunoki Susumu
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 89 Issue: 4 Pages: 435-437
  • DOI: 10.1136/jnnp-2017-316510
  • Peer Reviewed
• [Journal Article] Characterization of the neurological diseases associated with Mycoplasma pneumoniae infection and anti-glycolipid antibodies. (2017)
  • Author(s): Kuwahara M, Samukawa M, Ikeda T, Morikawa M, Ueno R, Hamada Y, Kusunoki S.
  • Journal Title: J Neurol Volume: 264 Issue: 3 Pages: 467-475
  • DOI: 10.1007/s00415-016-8371-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 4-Aminopyridine ameliorates experimental autoimmune neuritis in Lewis rats. (2017)
  • Author(s): Moriguchi K, Miyamoto K, Kusunoki S
  • Journal Title: J Neuroimmunol Volume: 305 Pages: 72-74
  • DOI: 10.1016/j.jneuroim.2017.01.023
  • Peer Reviewed
• [Journal Article] Serological study using glycoarray for detecting antibodies to glycolipids and glycolipid complexes in immune-mediated neuropathies. (2016)
  • Author(s): Morikawa M, Kuwahara M, Ueno R, Samukawa M, Hamada Y, Kusunoki S.
  • Journal Title: J Neuroimmunol Volume: 301 Pages: 35-40
  • DOI: 10.1016/j.jneuroim.2016.10.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Electrophysiological assessment of Guillain-Barré syndrome with both Gal-C and ganglioside antibodies; tendency for demyelinating type. (2016)
  • Author(s): Samukawa M, Kuwahara M, Morikawa M, Ueno R, Hamada Y, Takada K, Hirano M, Mitsui Y, Sonoo M, Kusunoki S.
  • Journal Title: J Neuroimmunol Volume: 301 Pages: 61-64
  • DOI: 10.1016/j.jneuroim.2016.10.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ganglionic acetylcholine receptor autoantibodies in patients with Guillain-Barre syndrome (2016)
  • Author(s): Nakane S, Higuchi O, Hamada Y, Maeda Y, Mukaino A, Sakai W, Kusunoki S, Matsuo H
  • Journal Title: J Neuroimmunol Volume: 295-296 Pages: 54-59
  • DOI: 10.1016/j.jneuroim.2016.04.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chondroitin sulfate β-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism; association with progression of multiple sclerosis. (2016)
  • Author(s): Saigoh, K., Yoshimura, S., Izumikawa, T., Miyata, S., Tabara, Y., Matsushita, T., Miki, T., Miyamoto, K., Hirano, M., Kitagawa, H., Kita, J., and Kusunoki, S.
  • Journal Title: Neurosci. Res. Volume: 印刷中 Pages: 55-59
  • DOI: 10.1016/j.neures.2016.01.002
  • Peer Reviewed
• [Journal Article] Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy. (2015)
  • Author(s): Ogata H, et al
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 10 Pages: 960-971
  • DOI: 10.1002/acn3.248
  • Peer Reviewed
• [Journal Article] CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy. (2015)
  • Author(s): Takahiro Furukawa, Naoko Matsui, Koji Fujita, Hiroyuki Nodera, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Yuishin Izumi, Ryuji Kaji,
  • Journal Title: Neurol Neuroimmunol Neuroinflamm Volume: 2 Issue: 5
  • DOI: 10.1212/nxi.0000000000000138
  • Peer Reviewed
• [Journal Article] Similarities of serum anti-ganglioside antibodies in first and third episodes of recurrent Guillain-Barré syndrome: case report. (2015)
  • Author(s): Togawa J, Nakaoku Y, Hagiwara M, Murakami G, Mitsueda-Ono T, Ueno R, Kusunoki S, Matsui M.
  • Journal Title: J Neurol Volume: 262 Issue: 5 Pages: 1360-1362
  • DOI: 10.1007/s00415-015-7714-7
  • Peer Reviewed
• [Journal Article] Keratan sulfate exacerbates experimental autoimmune encephalomyelitis. (2015)
  • Author(s): Ueno R, Miyamoto K, Tanaka N, Moriguchi K, Kadomatsu K, Kusunoki S.
  • Journal Title: J Neurosci Res. Volume: 93 Issue: 12 Pages: 1874-1880
  • DOI: 10.1002/jnr.23640
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Investigation of serum antibodies against glycolipids and glycolipid complexes in immune-mediated neuropathies by combinatorial glycoarray. (2017)
  • Author(s): Kusunoki S, Morikawa M, Kuwahara M, Ueno R, Samukawa M, Hamada Y.
  • Organizer: 2017 PNS Annual Meeting
  • Int'l Joint Research
• [Presentation] Differences of antibody reactivities against glycolipid complexes among Guillain-Barre syndrome, Miller Fisher syndrome and Bickerstaff brainstem encephalitis (2017)
  • Author(s): Yoshikawa K, Morikawa M, Kuwahara M, Kusunoki S
  • Organizer: 2017 PNS Annual Meeting
  • Int'l Joint Research
• [Presentation] Autoimmune neuropathy (2017)
  • Author(s): Kusunoki S
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research / Invited
• [Presentation] Antibody associated inflammatory neuropathies (2017)
  • Author(s): Kusunoki S
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research / Invited
• [Presentation] CIDP and associated antibodies (2017)
  • Author(s): Kusunoki S
  • Organizer: 142nd Annual Meeting of the American Neurological Association
  • Int'l Joint Research / Invited
• [Presentation] 免疫性神経疾患と自己抗体：Update (2017)
  • Author(s): 楠 進
  • Organizer: 第35回日本神経治療学会総会
  • Invited
• [Presentation] 神経免疫疾患研究の進歩 (2016)
  • Author(s): 楠 進
  • 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、米子
  • Year and Date: 2016-11-03
  • Invited
• [Presentation] Antiglycolipid antibodies in neurological diseases subsequent to Mycoplasma pneumoniae infection. (2016)
  • Author(s): Kusunoki S, Kuwahara M, Samukawa M, Morikawa M, Ueno R, Hamada Y.
  • Organizer: 141st Annual Meeting of American Neurological Association
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2016-10-16
  • Int'l Joint Research
• [Presentation] GBSの研究および診療における課題 (2016)
  • Author(s): 楠 進
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール、長崎
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] Gangliosides and anti-ganglioside antibodies. (2016)
  • Author(s): Kusunoki S
  • Organizer: Inflammatory Neuropathy Consortium 2016
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2016-06-21
  • Int'l Joint Research / Invited
• [Presentation] Electrophysiological assessment in Guillain-Barré syndrome with both anti-Gal-C and other ganglioside antibodies. (2016)
  • Author(s): Samukawa M, Kuwahara M, Ueno R, Hamada Y, Takada K, Hirano M, Mitsui Y, Sonoo M, Kusunoki S
  • Organizer: Inflammatory Neuropathy Consortium 2016
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2016-06-21
  • Int'l Joint Research
• [Presentation] 免疫性末梢神経障害 (2016)
  • Author(s): 楠 進
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2016-05-18
  • Invited
• [Presentation] Clinical and serological investigation of IgM paraproteinemic neuropathies without anti-MAG antibody activities. (2015)
  • Author(s): Kusunoki S, Kuwahara M, Hamada Y, Morikawa M, Ueno R, Samukawa M, Mitsui Y.
  • Organizer: XXII World Congress of Neurology
  • Place of Presentation: Santiago, Chile
  • Year and Date: 2015-10-31
  • Int'l Joint Research
• [Presentation] ギラン・バレー症候群と抗糖脂質抗体；AIDPに関連する抗体は？ (2015)
  • Author(s): 楠 進
  • Organizer: 第20回日本神経感染症学会学術大会
  • Place of Presentation: メルパルク長野、長野
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] グライコアレイを用いた免疫性ニューロパチーにおける血中糖脂質複合体抗体の解析. (2015)
  • Author(s): 森川みゆき, 上野莉乃, 寒川 真, 濱田征宏, 桑原 基, 楠 進.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ、新潟
  • Year and Date: 2015-05-19
• [Presentation] Combinatorial Glycoarrayによる網羅的抗糖脂質抗体の検出-ELISAとの比較 (2015)
  • Author(s): 桑原 基, 森川みゆき, 上野莉乃, 寒川 真, 濱田征宏, 楠 進.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ、新潟
  • Year and Date: 2015-05-19
• [Presentation] Antibodies to glycolipid and glycolipid complexes in GBS and related diseases. (2015)
  • Author(s): Kusunoki S
  • Organizer: Congress of Korean Neurological Association
  • Place of Presentation: Daegu, Korea
  • Year and Date: 2015-04-03
  • Int'l Joint Research / Invited