Analysis of granulocytes in inflammatory autoimmune disorders of the central nervous system

• Project/Area Number: 26461289
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: KAWACHI Izumi 新潟大学, 医歯学総合病院, 講師 (40432083)
• Co-Investigator(Kenkyū-buntansha): 豊島 靖子 新潟大学, 脳研究所, 准教授 (20334675)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 視神経脊髄炎 / 多発性硬化症 / アクアポリン４水チャネル / 顆粒球系細胞 / 神経病態免疫学

Outline of Final Research Achievements

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS). Accumulation of granulocytes, macrophages and tissue-resident lymphocytes was evident in early active lesions with a pattern-specific loss of aquaporin-4 (AQP4) immunoreactivities in NMOSD cases. These lesions had widespread neuroaxonal damage with axonal degenerative mitochondria, via abnormal AQP4 dynamics on astrocytes. These data suggest that unique dynamics of AQP4 autoantibodies and immune cells including granulocytes might cooperate to form massive damages of the CNS and cause severe physical and visual disabilities in NMOSD.

Research Products

• [Journal Article] Clinical characteristics of autoimmune optic neuritis. (2017)
  • Author(s): Kawachi I
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 8 (suppl. 1) Issue: S1 Pages: 8-16
  • DOI: 10.1111/cen3.12354
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinicopathological features in anterior visual pathway in neuromyelitis optica (2016)
  • Author(s): Hokari M, Yokoseki A, Arakawa M, Saji E, Yanagawa K, Yanagimura F, Toyoshima Y, Okamoto K, Ueki S, Hatase T, Ohashi R, Fukuchi T, Akazawa K, Yamada M, Kakita A, Takahashi H, Nishizawa M, Kawachi I.
  • Journal Title: Annals of Neurology Volume: 79 Issue: 4 Pages: 605-624
  • DOI: 10.1002/ana.24608
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neurodegeneration in multiple sclerosis and neuromyelitis optica. (2016)
  • Author(s): Kawachi I, Lassmann H.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 88 Issue: 2 Pages: 137-145
  • DOI: 10.1136/jnnp-2016-313300
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica (2016)
  • Author(s): Yamasaki R, Matsushita T, Fukazawa T, Yokoyama K, Fujihara K, Ogino M, Yokota T, Miyamoto K, Niino M, Nomura K, Tomioka R, Tanaka M, Kawachi I, Ohashi T, Kaida KI, Matsui M, Nakatsuji Y, Ochi H, Fukaura H, Kanda T, Nagaishi A, Togo K, Mizusawa H, Murai H, Kira JI
  • Journal Title: Multiple sclerosis Volume: 印刷中 Issue: 10 Pages: 1337-1348
  • DOI: 10.1177/1352458515617248
  • Peer Reviewed
• [Journal Article] Current treatment status and medical cost for multiple sclerosis based on analysis of a Japanese claims database (2016)
  • Author(s): Ogino M, Kawachi I, Otake K, Ohta H, Otsuka Y, Iwasaki K, Hiroi S
  • Journal Title: Clinical and experimental neuroimmunology Volume: 印刷中 Issue: 2 Pages: 158-167
  • DOI: 10.1111/cen3.12299
  • Peer Reviewed
• [Journal Article] Significance of gray matter brain lesions in multiple sclerosis and neuromyelitis optica (2015)
  • Author(s): Kawachi I, Nishizawa M
  • Journal Title: Neuropathology Volume: 35 Issue: 5 Pages: 481-486
  • DOI: 10.1111/neup.12216
  • Peer Reviewed
• [Journal Article] Immune-mediated hypertrophic pachymeningitis: clinical significance of ANCA and granulomatosis with polyangiitis (Wegener’s granulomatosis) (2014)
  • Author(s): Yokoseki A, Nishizawa M, Kawachi I
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 5 Issue: 3 Pages: 275-276
  • DOI: 10.1111/cen3.12117
  • Peer Reviewed
• [Journal Article] Deep grey matter involvement in multiple sclerosis: key player or bystander? (2014)
  • Author(s): Kawachi I
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 85 Issue: 12 Pages: 1293-1293
  • DOI: 10.1136/jnnp-2014-308221
  • Peer Reviewed
• [Journal Article] [A patient with granulomatosis with polyangiitis (Wegener's granulomatosis) presenting with diplopia and blepharoptosis: a case report] (2014)
  • Author(s): Kitahara M, Kanazawa M, Hatakeyama M, Yanagimura F, Sakagami T, Kawachi I, Nishizawa M
  • Journal Title: Brain Nerve Volume: 66 Pages: 880-881
  • Peer Reviewed
• [Journal Article] Can Anti-AQP4 Antibody Damage the Blood-Brain Barrier? (2014)
  • Author(s): Akaza M, Tanaka K, Tanaka M, Sekiguchi T, Misawa T, Nishina K, Kawachi I, Nishizawa M, Mizusawa H, Yokota T
  • Journal Title: European Neurology Volume: 72 Issue: 5-6 Pages: 273-277
  • DOI: 10.1159/000360619
  • Peer Reviewed
• [Presentation] NMO is characterized by serious attacks and neurodegeneration with abnormal mitochondria. (2016)
  • Author(s): Hokari M, Yokoseki A, Saji E, Arakawa M, Yanagawa K, Yanagimura F, Toyoshima Y, Kakita A, Takahashi H, Nishizawa M, Kawachi I.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター (兵庫県神戸市)
  • Year and Date: 2016-05-18
• [Presentation] Severe neurodegeneration and unique dynamics of astrocytes/Muller cells with alterations of aquaporin-4 in neuromyelitis optica (2016)
  • Author(s): Kawachi I, Hokari M, Yokoseki A, Arakawa M, Saji E, Yanagawa K, Yanagimura F, Toyoshima Y, Kakita A, Takahashi H, Nishizawa M
  • Organizer: 8th Annual Neuromyelitis optica roundtable conference (Guthy Jackson Charitable Foundation)
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2016-02-29
  • Int'l Joint Research / Invited
• [Presentation] シンポジウム4「認知症と神経免疫」. (3) 多発性硬化症と視神経脊髄炎における認知機能障害と神経変性 (2015)
  • Author(s): 河内泉, 西澤正豊
  • Organizer: 第27回神経免疫学会学術集会
  • Place of Presentation: 長良川国際会議場 (岐阜県岐阜市)
  • Year and Date: 2015-09-15
  • Invited
• [Presentation] 神経病理学におけるベストエビデンス;中枢神経系自己免疫疾患におけるベストエビデンス(Best evidence of autoimmune CNS diseases) (2015)
  • Author(s): 河内泉, 西澤正豊
  • Organizer: 第56回日本神経病理学会学術研究会
  • Place of Presentation: 九州大学医学部百年講堂 (福岡県福岡市)
  • Year and Date: 2015-06-03
  • Invited
• [Presentation] Immunopathology of NMO (2015)
  • Author(s): Kawachi I, Nishizawa M
  • Organizer: 第56回日本神経学会学術集会
  • Place of Presentation: 朱鷺メッセ (新潟県新潟市)
  • Year and Date: 2015-05-20
  • Invited
• [Presentation] Clinical and radiological profiles of anterior visual pathway involvement in neuromyelitis optica (2014)
  • Author(s): Izumi Kawachi, Akiko Yokoseki, Etsuji Saji, Mariko Hokari, Kaori Yanagawa, Masatoyo Nishizawa
  • Organizer: 2014 Joint ACTRIMS-ECTRIMS Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] シンポジウム「MS vs NMO (疾患を裏側から見る)」細胞性免疫機構からみたNMO (2014)
  • Author(s): 河内泉
  • Organizer: 第26回神経免疫学会
  • Place of Presentation: 金沢, 金沢歌劇座
  • Year and Date: 2014-09-04 – 2014-09-06
  • Invited
• [Presentation] ワークショップ: MS、NMO そして PML の神経病理学の新たな展開. 視神経脊髄炎と多発性硬化症の大脳皮質病変とその臨床的意義 (2014)
  • Author(s): 河内泉
  • Organizer: 第55回日本神経病理学会
  • Place of Presentation: 東京, 学術総合センター
  • Year and Date: 2014-06-05 – 2014-06-07
  • Invited
• [Presentation] シンポジウム: MSの高次脳機能障害. 多発性硬化症における灰白質病変 -認知機能障害の観点から- (2014)
  • Author(s): 河内泉
  • Organizer: 第55回日本神経学会
  • Place of Presentation: 福岡, 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
  • Invited
• [Presentation] シンポジウム: 肥厚性硬膜炎をめぐる最近の進歩:ANCA関連血管炎とIgG4関連 疾患の病態に焦点をあてて. ANCA関連血管炎における肥厚性硬膜炎 -新しい概念と免疫病態- (2014)
  • Author(s): 河内泉
  • Organizer: 第55回日本神経学会
  • Place of Presentation: 福岡, 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-24
  • Invited
• [Book] 多発性硬化症の「炎症・変性」と進行型多発性硬化症に対する治療の最新動向. Annual Review 神経2017 (2017)
  • Author(s): 河内泉
  • Total Pages: 9
  • Publisher: 中外医学社
• [Book] III. 免疫を治す－治療薬・治療法. 免疫抑制薬. アクチュアル脳・神経疾患の臨床. 免疫性神経疾患―病態と治療のすべて (2016)
  • Author(s): 河内泉, 西澤正豊
  • Total Pages: 12
  • Publisher: 中山書店
• [Book] 第4章 眼窩・眼瞼・全身疾患. C. 肥厚性硬膜炎. 眼科臨床エキスパートシリーズ. 知っておきたい神経眼科診療 (2016)
  • Author(s): 河内泉, 西澤正豊
  • Total Pages: 10
  • Publisher: 医学書院
• [Book] その他の免疫疾患を含めて- I. 臓器特異的自己免疫疾患 免疫性神経・筋疾患, 自己免疫性脳炎・脳症, AMPA受容体抗体脳炎. 免疫症候群I (第2版) 別冊日本臨床 領域別症候群シリーズ (2015)
  • Author(s): 河内泉, 西澤正豊
  • Total Pages: 3
  • Publisher: 日本臨床社
• [Book] II. 免疫性中枢神経疾患 視神経脊髄炎 (NMO), NMO spectrum disorder. 免疫性神経疾患-基礎・臨床研究の最新知見 (2015)
  • Author(s): 河内泉, 西澤正豊
  • Total Pages: 4
  • Publisher: 日本臨床社
• [Remarks] 新潟大学脳研究所ホームページ
  • URL: http://www.bri.niigata-u.ac.jp
• [Remarks] 新潟大学ホームページ
  • URL: http://www.niigata-u.ac.jp
• [Remarks] 新潟大学脳研究所神経内科ホームページ
  • URL: http://www.neurology-bri.jp