中枢神経系脱髄疾患におけるＩ型インターフェロンの動態とその制御機構の解析

2013 年度 研究成果報告書

• 研究課題/領域番号: 23591236
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 神経内科学
• 研究機関: 新潟大学
• 研究代表者: 河内 泉 新潟大学, 医歯学総合病院, 助教 (40432083)
• 研究分担者: 豊島 靖子 新潟大学, 脳研究所, 准教授 (20334675)
• 研究期間 (年度): 2011 – 2013
• キーワード: 視神経脊髄炎 / 多発性硬化症 / 自然免疫機構 / アクアポリン4水チャネル

研究概要

視神経器脊髄炎 (NMO) は長い間, 多発性硬化症との異同が論じられてきたが, 疾患特異的自己抗体の発見により, アクアポリン4 (AQP4) を標的とするアストロサイトパチーであることが明らかにされた. (1) NMO病巣ではAQP4発現低下, 血管周囲の免疫グロブリン/補体沈着に加え, 顆粒球, マクロファージ, 形質/形質芽細胞, 抗原提示細胞の増生を認め, (2) NMO末梢血では多数の形質芽細胞を認め, (3) NMOのヘルパーT細胞はIL-17/IFN-γ産生に偏奇していた. NMOでは独特の自然免疫システムを使うことで, 特徴的な自己免疫病態を形成する可能性が示唆された.

研究成果

• [雑誌論文] Hypertrophic pachymeningitis : significance of myeloperoxidase anti-neutrophil cytoplasmic antibody (2014)
  • 著者名/発表者名: Yokoseki A, Saji E, Arakawa M, Kosaka T, Hokari M, Toyoshima Y, Okamoto K, Takeda S, Sanpei K, Kikuchi H, Hirohata S, Akazawa K, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 雑誌名: Brain 巻: 137(2) ページ: 520-536
  • DOI: 10.1093/brain/awt314
  • 査読あり
• [雑誌論文] Gray matter involvement in multiple sclerosis and neuromyelitis optica (2014)
  • 著者名/発表者名: Kawachi I, Nishizawa M
  • 雑誌名: Clinical and Experimental Neuroimmunology 巻: 5(1) ページ: 69-76
  • DOI: 10.1111/cen3.12077
  • 査読あり
• [雑誌論文] Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis (2014)
  • 著者名/発表者名: Niino M, Mifune N, Kohriyama T, Mori M, Ohashi T, Kawachi I, Shimizu Y, Fukaura H, Nakashima I, Kusunoki S, Miyamoto K, Yoshida K, Kanda T, Nomura K, Yamamura T, Yoshii F, Kira J, Nakane S, Yokoyama K, Matsui M, Miyazaki Y, Kikuchi S
  • 雑誌名: BMC Neurology 巻: 14(1) ページ: 3
  • DOI: 10.1186/1471-2377-14-3
  • 査読あり
• [雑誌論文] Cognitive impairment and cortical degeneration in neuromyelitis optica (2013)
  • 著者名/発表者名: Saji E, Arakawa M, Yanagawa K, Toyoshima Y, Yokoseki A, Okamoto K, Otsuki M, Akazawa K, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 雑誌名: Annals of Neurology 巻: 73(1) ページ: 65-76
  • DOI: 10.1002/ana.23721
  • 査読あり
• [雑誌論文] Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis : an observational cohort study (2013)
  • 著者名/発表者名: Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Arribas NG A, Rosenfeld MR, Gordon BR, Graus F, Dalmau J
  • 雑誌名: Lancet Neurology 巻: 12(2) ページ: 157-65
  • DOI: 10.1016/S1474-4422(12)70310-1
  • 査読あり
• [雑誌論文] Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy (2013)
  • 著者名/発表者名: Yokoseki A, Saji E, Arakawa M, Hokari M, Ishiguro T, Yanagimura F, Ishihara T, Okamoto K, Nishizawa M, Kawachi I
  • 雑誌名: Multiple Sclerosis Journal 巻: 19(9) ページ: 1230-1233
  • DOI: 10.1177/1352458513481395
  • 査読あり
• [雑誌論文] T lymphocytes : Helpers (2013)
  • 著者名/発表者名: Kawachi I, Kondo T
  • 雑誌名: ENCYCLOPEDIA OF LIFE SCIENCES 2013 巻: (Published online)
  • DOI: 10.1002/9780470015902.a0001224.pub3
  • 査読あり
• [雑誌論文] Late-onset anti-NMDA receptor encephalitis (2013)
  • 著者名/発表者名: Titulaer MJ, McCracken L, Gabilondo I, Iizuka T, Kawachi I, Bataller L, Torrents A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J
  • 雑誌名: Neurology 巻: 81(12) ページ: 1058-1063
  • DOI: 10.1212/WNL.0b013e3182a4a49c
  • 査読あり
• [雑誌論文] Efficacy of methylprednisolone pulse therapy for acute relapse in Japanese patients with multiple sclerosis and neuromyelitis optica : a multicenter retrospective analysis : 1. Whole group analysis (2013)
  • 著者名/発表者名: Kira J, Yamasaki R, Yoshimura S, Fukazawa T, Yokoyama K, Fujihara K, Ogino M, Yokota T, Miyamoto K, Niino M, Nomura K, Tomita R, Tanaka M, Kawachi I, Ohashi T, Kaida K, Matsui M, Nakatsuji Y, Ochi H, Kanda T, Nagaishi A, Togo K, Mizusawa H, Kawano Y
  • 雑誌名: Clinical and Experimental Neuroimmunology 巻: 4(3) ページ: 305-317
  • DOI: 10.1111/cen3.12071
  • 査読あり
• [雑誌論文] 多発性硬化症・視神経脊髄炎における認知機能障害.多発性硬化症の新展開 (2013)
  • 著者名/発表者名: 河内泉,西澤正豊
  • 雑誌名: 脳21 巻: 16(4) ページ: 454-459
• [雑誌論文] 視神経脊髄炎には認知機能障害と大脳皮質変性が存在する (2013)
  • 著者名/発表者名: 河内泉
  • 雑誌名: MS Frontier 巻: 2(2) ページ: 22-25
• [雑誌論文] Dropped head syndrome in amyotrophic lateral sclerosis (2013)
  • 著者名/発表者名: Uemura M, Kosaka T, Shimohata T, Ishikawa M, Nishihira Y, Toyoshima Y, Yanagawa K, Kawachi I, Takahashi H, Nishizawa M
  • 雑誌名: Amyotroph Lateral Scler Frontotemporal Degener 巻: 14 ページ: 232-3
  • DOI: 10.3109/17482968.2012.727424
  • 査読あり
• [雑誌論文] Chorea as the first sign in a patient with elderly-onset systemic lupus erythematosus (2012)
  • 著者名/発表者名: Ariizumi Y, Ozawa T, Tokutake T, Kawachi I, Hirose M, Katada S, Igarashi S, Tanaka K, Nishizawa M
  • 雑誌名: Case reports in neurological medicine 巻: 2012 ページ: 317082
  • DOI: 10.1155/2012/317082
  • 査読あり
• [雑誌論文] Successful treatment of neuroborreliosis with combined administration of antibiotics and steroids : A case report (2012)
  • 著者名/発表者名: Takado Y, Shimohata T, Kawachi I, Tanaka K, Nishizawa M
  • 雑誌名: Rinsho Shinkeigaku 巻: 52(6) ページ: 411-5
  • 査読あり
• [雑誌論文] Neuromyelitis optica following thymectomy with severe spinal cord atrophy after frequent relapses for 30 years (2012)
  • 著者名/発表者名: Hironishi M, Ishimoto S, Sawanishi T, Miwa H, Kawachi I, Kondo T
  • 雑誌名: Brain Nerve 巻: 64(8) ページ: 951-5
  • 査読あり
• [雑誌論文] Semiquantitative measurement of aquaporin-4 antibodies as a possible surrogate marker of neuromyelitis optica spectrum disorders with systemic autoimmune diseases (2012)
  • 著者名/発表者名: Katsumata Y, Kawachi I, Kawaguchi Y, Gono T, Ichida H, Hara M, Yamanaka H
  • 雑誌名: Mod Rheumatol 巻: 22(5) ページ: 676-84
  • 査読あり
• [雑誌論文] A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans (2011)
  • 著者名/発表者名: Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K
  • 雑誌名: J Clin Invest 巻: 121 ページ: 4150-60
  • 査読あり
• [雑誌論文] A case of inflammatory myopathy with widely skin rash following use of supplements containing Spirulina (2011)
  • 著者名/発表者名: Konno T, Umeda Y, Umeda M, Kawachi I, Oyake M, Fujita N
  • 雑誌名: Rinsho Shinkeigaku 巻: 51 ページ: 330-3
  • 査読あり
• [雑誌論文] アクアポリン4抗体 (2011)
  • 著者名/発表者名: 西澤正豊,河内泉
  • 雑誌名: SRL宝函 巻: 32(2) ページ: 4-12
• [学会発表] Optic Perineuritis-like Lesions in Neuromyelitis Optica : Radiological Assessments (2013)
  • 著者名/発表者名: Yokoseki A, Saji E, Arakawa M, Hokari M, Nishizawa M, Kawachi I
  • 学会等名: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Kyoto, Japan
  • 年月日: 2013-11-07
• [学会発表] Neuromyelitis Optica with Severe Progressive Cognitive and Psychiatric Impairment : Pathological Analysis of Three Autopsied Cases (2013)
  • 著者名/発表者名: Arakawa M, Saji E, Toyoshima Y, Hokari M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 学会等名: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Kyoto, Japan
  • 年月日: 2013-11-07
• [学会発表] Radiological and Pathological Analyses of Cortical Lesions in Inflammatory Demyelinating Diseases of the Central Nervous System (2013)
  • 著者名/発表者名: Saji E, Arakawa M, Yokoseki A, Hokari M, Toyoshima Y, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 学会等名: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Kyoto, Japan
  • 年月日: 2013-11-07
• [学会発表] Clinical Profiles of Elderly Patients with ADEM in A Japanese Cohort (2013)
  • 著者名/発表者名: Hokari M, Saji E, Yokoseki A, Arakawa M, Nishizawa M, Kawachi I
  • 学会等名: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Kyoto, Japan
  • 年月日: 2013-11-07
• [学会発表] Paraneoplastic Anti-NMDA Receptor Encephalitis Presenting With Neuromyelitis Optica-Like Relapses (2013)
  • 著者名/発表者名: Yanagimura F, Kawachi I, Saji E, Hokari M, Yokoseki A, Arakawa M, Nishizawa M
  • 学会等名: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Kyoto, Japan
  • 年月日: 2013-11-07
• [学会発表] Longitudinal flow cytometric profiles of immune cells in the cerebrospinal fluid and blood of patients with multiple sclerosis under fingolimod therapy (2013)
  • 著者名/発表者名: Kawachi I, Yokoseki A, Saji E, Arakawa M, Hokari M, Nishizawa M
  • 学会等名: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Copenhagen, Denmark
  • 年月日: 2013-10-04
• [学会発表] CNS pathology in neuromyelitis optica : region-dependent dynamics of aquaporin-4 (2013)
  • 著者名/発表者名: Arakawa M, Saji E, Toyoshima Y, Hokari M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 学会等名: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Copenhagen, Denmark
  • 年月日: 2013-10-04
• [学会発表] Characteristic features of inflammatory demyelination and neurodegeneration in neuromyelitis optica spectrum disorder (2012)
  • 著者名/発表者名: Arakawa M, Toyosima Y, Saji E, Yanagawa K, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 学会等名: The 11th International Congress of Neuroimmunology
  • 発表場所: Boston, USA
  • 年月日: 2012-11-07
• [学会発表] Potential role of CCR6+ T cells in inflammatory demyelinating diseases of central nervous system (2012)
  • 著者名/発表者名: Saji E, Arakawa M, Hokari M, Toyosima Y, Yanagawa K, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • 学会等名: The 11th International Congress of Neuroimmunology
  • 発表場所: Boston, USA
  • 年月日: 2012-11-06
• [学会発表] Diagnostic dilemma of Japanese patients with AQP4 antibody (2012)
  • 著者名/発表者名: Kawachi I, Yanagawa K, Saji E, Yokoseki A, Hokari M, Nishizawa M
  • 学会等名: The 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Lion, France
  • 年月日: 2012-10-11
• [学会発表] Possible role of subarachnoid space as the initiating site for triggering the immune-mediated injury in CNS demyelinating diseases (2012)
  • 著者名/発表者名: Kawachi I, Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Hokari M, Kakita A, Takahashi H, Nishizawa H
  • 学会等名: The 5th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Beijing, China
  • 年月日: 2012-09-15
• [学会発表] Characteristic features of cognitive dysfunction in neuromyelitis optica and multiple sclerosis (2012)
  • 著者名/発表者名: Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Hokari M, Nishizawa M, and Kawachi I
  • 学会等名: The 5th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Beijing, China
  • 年月日: 2012-09-14
• [学会発表] Absence of meningeal lymphoid neogenesis in neuromyelitis optica (2011)
  • 著者名/発表者名: Kawachi I, Yanagawa K, Toyoshima Y, Saji E, Arakawa M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M
  • 学会等名: The 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Amsterdam, The Netherlands
  • 年月日: 2011-10-21
• [学会発表] Possible association of retinal nerve fiber layer thinning with cognitive dysfunction in neuromyelitis optica (2011)
  • 著者名/発表者名: Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Nishizawa M, Kawachi I
  • 学会等名: The 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis
  • 発表場所: Amsterdam, The Netherlands
  • 年月日: 2011-10-21
• [図書] III.視神経脊髄炎の病態と治療. NMO spectrum disorder.アクチュアル脳・神経疾患の臨床.多発性硬化症と視神経脊髄炎 (2012)
  • 著者名/発表者名: 河内泉,西澤正豊
  • 総ページ数: 331-337
  • 出版者: 中山書店.東京
• [図書] II. MSとNMOの基礎. 2.免疫制御のキープレイヤーとネットワーク.多発性硬化症(MS)と視神経脊髄炎(NMO)の基礎と臨床 (2012)
  • 著者名/発表者名: 河内泉
  • 総ページ数: 33-45
  • 出版者: 医薬ジャーナル社.東京
• [図書] III.認知症をきたす疾患.多発性硬化症.アクチュアル脳・神経疾患の臨床.認知症神経心理学的アプローチ (2012)
  • 著者名/発表者名: 河内泉,西澤正豊
  • 総ページ数: 256-270
  • 出版者: 中山書店.東京
• [備考] 新潟大学脳研究所神経内科学分野
  • URL: http://www.bri.niigata-u.ac.jp