Elucidation of molecular basis and therapeutic strategy of immune-mediated neurological diseases based on comprehensive analysis of autoantibodies

• Project/Area Number: 23249048
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: TSUJI Shoji 東京大学, 医学部附属病院, 教授 (70150612)
• Co-Investigator(Kenkyū-buntansha): GOSHIMA Naoki 産業技術総合研究所, 主任研究員 (70215482) ; KUSUNOKI Susumu 近畿大学, 医学部, 教授 (90195438) ; TANAKA Keiko 金沢医科大学, 医学部, 教授 (30217020)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Jun 東京大学, 医学部附属病院, 講師 (40260492)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥48,100,000 (Direct Cost: ¥37,000,000、Indirect Cost: ¥11,100,000); Fiscal Year 2013: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2012: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2011: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
• Keywords: 神経病態免疫学 / プロテインアレイ / 免疫性神経疾患 / 自己抗体 / プロファイリング / 傍腫瘍性症候群

Research Abstract

Employing active protein arrays containing recombinant proteins with preserved native structures, sera from 20 patients with paraneoplastic cerebellar degeneration, immune-mediated encephalitis, acute autonomic neuronopathy, and immune-mediated myosisit are subjected to comprehensive antigen screening. Forty to 60 antigens were recognized by the individual serum. Search for homologous regions among the antigens recognized by the same serum revealed that the eiptopes are not shared among these antigens.

Research Products

• [Journal Article] Anti-NMDA Receptor Encephalitis Associated With Transient Cerebral Dyschromatopsia (2014)
  • Author(s): Sawamura H, Yamamoto T, Ohtomo R, Bannai T, Wakakura M, Tsuji S
  • Journal Title: Prosopagnosia, and Lack of Stereopsis. J. Neuro-ophthalmol Volume: 34 Pages: 144-8
• [Journal Article] Transient cerebral dyschromatopsia, prosopagnosia, and dysfunction of stereopsis in association with anti-NMDA receptor encephalitis. (2014)
  • Author(s): Sawamura H, Yamamoto T, Ohtomo R, Bannai T, Wakakura M, and Tsuji S
  • Journal Title: J. Neuro-Ophthalmol. Volume: in press Issue: 2 Pages: 144-148
  • DOI: 10.1097/wno.0000000000000117
  • Peer Reviewed
• [Journal Article] Autoantibodies in neuroimmunological diseases; relevance of fine specificity (2013)
  • Author(s): Kusunoki S
  • Journal Title: Exp. Neurol Volume: 250 Pages: 219-20
• [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. Psychiat Volume: 84 Pages: 573-5
• [Journal Article] Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type (2013)
  • Author(s): Tetsuka S, Tominaga K, Ohta E, Kuroiwa K, Sakashita E, Kasashima K, Hamamoto T, Namekawa M, Morita M, Natsui S, Morita T, Tanaka K, Takiyama Y, Nakano I, Endo H
  • Journal Title: J. Neurol. Sci Volume: 335 Pages: 48-57
• [Journal Article] Integrated view of the human chromosome X-centric proteome project (2013)
  • Author(s): Yamamoto T, Nakayama K, Hirano H, Tomonaga T, Ishihama Y, Yamada T, Kondo T, Kodera Y, Sato Y, Araki N, Mamitsuka H, Goshima N
  • Journal Title: J. Proteome Res Volume: 12 Pages: 58-61
• [Journal Article] Autoantibodies in neuroimmunological diseases; relevance of fine specificity (2013)
  • Author(s): Kusunoki, S.
  • Journal Title: Exp Neurol Volume: 250 Pages: 219-220
  • DOI: 10.1016/j.expneurol.2013.10.009
  • 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] Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type (2013)
  • Author(s): Tetsuka, S. Tominaga, K. Ohta, E. Kuroiwa, K. Sakashita, E. Kasashima, K. Hamamoto, T. Namekawa, M. Morita, M. Natsui, S. Morita, T. Tanaka, K. Takiyama, Y. Nakano, I. Endo, H.
  • Journal Title: J Neurol Sci Volume: 335 Issue: 1-2 Pages: 48-57
  • DOI: 10.1016/j.jns.2013.08.022
  • Peer Reviewed
• [Journal Article] Integrated view of the human chromosome X-centric proteome project. (2013)
  • Author(s): Yamamoto T, Nakayama K, Hirano H, Tomonaga T, Ishihama Y, Yamada T, Kondo T,Kodera Y, Sato Y, Araki N, Mamitsuka H, Goshima N.
  • Journal Title: J Proteome Res. Volume: 12 Issue: 1 Pages: 58-61
  • DOI: 10.1021/pr300844p
  • Peer Reviewed
• [Journal Article] Aberrant expression of myogenin in inclusion body myositis: Immunohistochemical studies of transcription factors regulating myogenesis in inflammatory myopathies. (2012)
  • Author(s): Kubota A, Shimizu J, Iwata A, Tsuji S.
  • Journal Title: Clin Exp Neuroimmunol Volume: 3 Issue: 3 Pages: 129-137
  • DOI: 10.1111/cen3.12000
  • 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
• [Journal Article] Suppression of synaptic plasticity by cerebrospinal fluid from anti-NMDA receptor encephalitis patients (2012)
  • Author(s): Zhang Q
  • Journal Title: Neurobiol Dis. Volume: 45(1) Issue: 1 Pages: 610-615
  • DOI: 10.1016/j.nbd.2011.09.019
  • Peer Reviewed
• [Journal Article] Inflammatory myopathies associated with anti-mitochondrial antibodies (2012)
  • Author(s): Hashimoto-Maeda M, Tsuji S, Shimizu J
  • Journal Title: Brain Volume: (In press)
  • Peer Reviewed
• [Journal Article] Relationship between NMO-antibody and anti-MOG antibody in opticneuritis (2012)
  • Author(s): Kezuka T, Usui Y, Yamakawa N, Matsunaga Y, Matsuda R, Masuda M, Utsumi H, Tanaka K, Goto H
  • Journal Title: J Neuroophthalmol Volume: (In press)
  • Peer Reviewed
• [Journal Article] Antibodies against ganglioside complexes in Guillain-Barre syndrome and related disorders (2011)
  • Author(s): Kusunoki, S., K.Kaida
  • Journal Title: J.Neurochem. Volume: 116 Pages: 828-832
  • Peer Reviewed
• [Journal Article] Antibodies to LM1 and LM1-containing ganglioside complexes in Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy (2011)
  • Author(s): Kuwahara M, Suzuki S, Takada K, Kusunoki S
  • Journal Title: J Neuroimmunol. Volume: 239 Pages: 87-90
  • Peer Reviewed