Analysis of negative regulators of B lymphocyte responses to glycoconjugates in neuroimmunological diseases

• Project/Area Number: 24390225
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kinki University
• Principal Investigator: KUSUNOKI Susumu 近畿大学, 医学部, 教授 (90195438)
• Co-Investigator(Kenkyū-buntansha): SAIGOH Kazumasa 近畿大学, 医学部, 講師 (50319688) ; HIRANO Makito 近畿大学, 医学部・附属病院, 准教授 (50347548) ; MIYAMOTO Katsuichi 近畿大学, 医学部, 准教授 (50388526)
• Co-Investigator(Renkei-kenkyūsha): TSUBATA Takeshi 東京医科歯科大学, 大学院・疾患生命科学研究部, 教授 (80197756)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 糖鎖 / 自己免疫 / 神経疾患 / 糖脂質 / ガングリオシド / 硫酸化糖脂質 / 脱髄 / ギラン・バレー症候群 / シアル酸 / ミエリン / 自己抗体

Outline of Final Research Achievements

Gene analysis of the molecules regulating immunological reactions to glycoconjugates were investigated in neuroimmunological diseases with anti-glycolipid antibodies. Mutations were detected in such molecules specifically in some cases of Guillain-Barre syndrome (GBS). Patients with CIDP having antibodies to LM1-associated antigens rarely had cranial neuropathies and frequently had ataxia. GBS cases with antibodies to Gal-C, a myelin antigen, more frequently were classified as demyelinating type. In IgM paraproteinemic neuropathies, specificities of IgM M-proteins were associated with the clinical features.

Research Products

• [Journal Article] Binding specificity of anti-HNK-1 IgM M-protein in anti-MAG neuropathy: Possible clinical relevance. (2015)
  • Author(s): Hamada Y, Hirano M, Kuwahara M, Samukawa M, Takada K, Morise J, Yabuno K, Oka S, and Kusunoki S.
  • Journal Title: Neurosci Res. Volume: 91 Pages: 63-68
  • DOI: 10.1016/j.neures.2014.09.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical features in Guillain-Barré syndrome with anti-Gal-C antibody. (2014)
  • Author(s): Samukawa M, Hamada Y, Kuwahara M, Takada K, Hirano M, Mitsui Y, Sonoo M, Kusunoki S, the Japanese GBS Study Group.
  • Journal Title: J Neurol Sci Volume: 337 Issue: 1-2 Pages: 55-60
  • DOI: 10.1016/j.jns.2013.11.016
  • Peer Reviewed
• [Journal Article] A multicenter prospective study of Guillain-Barré syndrome in Japan: a focus on the incidence of subtypes. (2013)
  • Author(s): Mitsui Y, Kusunoki S, Arimura K, Kaji R, Kanda T, Kuwabara S, Sonoo M, Takada K, the Japanese GBS Study Group.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: on line Issue: 1 Pages: 110-114
  • DOI: 10.1136/jnnp-2013-306509
  • Peer Reviewed
• [Journal Article] Clinical features of CIDP with LM1-associated antibodies (2013)
  • Author(s): Kuwahara M, Suzuki H, Samukawa M, Hamada Y, Takada K, Kusunoki S.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84 Issue: 5 Pages: 573-575
  • DOI: 10.1136/jnnp-2012-303440
  • Peer Reviewed
• [Journal Article] Effects of acidic phospholipids on antiganglioside antibodies in GBS : roL of the disialosyl residue. (2013)
  • Author(s): Yamada M, Masami U, Tsuji S, Kusunoki S.
  • Journal Title: Clin Exp Neuroimmuno1 Volume: (in press) Issue: 1 Pages: 70-74
  • DOI: 10.1111/cen3.12002
  • Peer Reviewed
• [Journal Article] An antibody to the GM1/GalNAc-GD1a complex correlates with development of pure motor Guillain-Barre syndrome with reversible conduction failure. (2012)
  • Author(s): Ogawa, G., Kaida, K., Kuwahara, M., Kimura, F., Kamakura, K. and Kusunoki, S.
  • Journal Title: J Neuroimmunol Volume: 254 Issue: 1-2 Pages: 141-145
  • DOI: 10.1016/j.jneuroim.2012.09.005
  • Peer Reviewed
• [Presentation] Antibodies to gangliosides and ganglioside complexes in autoimmune neuropathies. (2014)
  • Author(s): Kusunoki S
  • Organizer: 13th Surugadai International Symposium & Joint Usage/Research Program of Medical Research Institute International Symposium
  • Place of Presentation: 東京（東京医科歯科大学）
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] 病原微生物とギラン・バレー症候群 (2014)
  • Author(s): 楠 進
  • Organizer: 第19回日本神経感染症学会総会学術集会・第26回日本神経免疫学会学術集会
  • Place of Presentation: 金沢（金沢歌劇座）
  • Year and Date: 2014-09-04 – 2014-09-06
  • Invited
• [Presentation] Electrophysiological subtypes of GBS with anti-Gal-C antibodies and other anti-glycolipid antibodies (2014)
  • Author(s): Kusunoki S, Samukawa M, Hamada, Y, Kuwahara M, Takada K, Hirano M, Mitsui Y.
  • Organizer: Inflammatory Neuropathy Consortium
  • Place of Presentation: Dusseldorf, Germany
  • Year and Date: 2014-07-12 – 2014-07-16
• [Presentation] 免疫性神経疾患と糖脂質に対する自己抗体 (2014)
  • Author(s): 楠 進
  • Organizer: 第56回日本脂質生化学会
  • Place of Presentation: 大阪（近畿大学）
  • Year and Date: 2014-06-06 – 2014-06-07
  • Invited
• [Presentation] 免疫性ニューロパチーの病態と治療の最前線 (2014)
  • Author(s): 楠 進
  • Organizer: 第111回日本内科学会講演会
  • Place of Presentation: 東京（東京フォーラム）
  • Year and Date: 2014-04-11 – 2014-04-13
  • Invited
• [Presentation] The incidence of subtypes of Guillain-Barré syndrome; Japanese multi-center prospective study. (2013)
  • Author(s): Kusunoki S, Mitsui Y, Arimura K, Kaji R, Kanda T, Kuwabara S, Sonoo M, Takada K.
  • Organizer: 2013 Annual Meeting of the American Neurological Association
  • Place of Presentation: New Orleans, USA
• [Presentation] 免疫性末梢神経疾患の病態と自己抗体。 (2013)
  • Author(s): 楠 進
  • Organizer: 第41回日本臨床免疫学会総会
  • Place of Presentation: 下関
  • Invited
• [Presentation] 免疫性ニューロパチーと抗糖脂質抗体。 (2013)
  • Author(s): 楠 進
  • Organizer: 第18回日本神経感染症学会総会
  • Place of Presentation: 宮崎
  • Invited
• [Presentation] 抗galactocerebroside抗体陽性Guillain-Barré症候群の臨床的、電気生理学的検討。 (2013)
  • Author(s): 600. 寒川 真、濱田征宏、桑原 基、鈴木秀和、高田和男、三井良之、楠 進。
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] ギラン・バレー症候群、フィッシャー症候群 診療ガイドライン (2013)
  • Author(s): 楠 進
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] シンポジウム「なぜそこが障害されるのか : 末梢神経障害部位を決める分子メカニズム」-免疫学の視点から : ギラン・バレー症候群とフィッシャー症候群において抗ガングリオシド抗体の結合を規定する因子は何か (2012)
  • Author(s): 楠進
  • Organizer: 第23回日本末梢神経学会学術集会
  • Place of Presentation: ホテル日航福岡(福岡市)(招待講演)
• [Presentation] Anti-ganglioside antibodies in inflammatory neuropathies. (2012)
  • Author(s): Kusunoki S.
  • Organizer: PNS/Inflammatory Neuropathy Consortium.
  • Place of Presentation: Lantaren Venster, Rotterdam, The Netherlands(招待講演)