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High-mobility group box 1 is involved in neuromyelitis optica pathogensesis and could be a therapeutic target.

Research Project

Project/Area Number 24790873
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionChiba University

Principal Investigator

UZAWA Akiyuki  千葉大学, 医学部附属病院, 助教 (10533317)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords視神経脊髄炎 / HMGB1 / サイトカイン / 多発性硬化症 / 実験的自己免疫性脳脊髄炎 / 自己免疫疾患 / モノクローナル抗体 / 血液脳関門 / モデル動物 / GFAP
Research Abstract

Cerebrospinal fluid (CSF) high-mobility group box 1 (HMGB1) levels in neuromyelitis optica (NMO) patients were significantly higher than those in multiple sclerosis (MS) and controls patients. In addition, CSF HMGB1 levels significantly correlated with CSF cell counts, protein levels, interleukin-6 levels, glial fibrillary acidic protein levels and CSF/serum albumin ratio in NMO. Administration of an anti-HMGB1 monoclonal antibody ameliorated the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE) and attenuated serum interleukin-17 up-regulation. HMGB1 could play a key role in central nervous system inflammation in NMO patients and EAE. HMGB1 could be a novel therapeutic strategy for NMO.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 12 results) Presentation (12 results) Remarks (3 results)

  • [Journal Article] Serum Cytokine and Chemokine Profiles in Patients with Myasthenia Gravis2014

    • Author(s)
      Uzawa A, Kawaguchi N, Himuro K, Kanai T, Kuwabara S
    • Journal Title

      Clin Exp Immunol.

      Volume: (in press) Issue: 2 Pages: 232-237

    • DOI

      10.1111/cei.12272

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cytokines and chemokines in neuromyelitis optica: pathogenetic and therapeutic implications.2014

    • Author(s)
      Uzawa A, Mori M, Kuwabara S
    • Journal Title

      Brain Pathol

      Volume: 24 Issue: 1 Pages: 67-73

    • DOI

      10.1111/bpa.12097

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] "Bright spotty lesions" on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis.2014

    • Author(s)
      Yonezu T, Ito S, Mori M, Ogawa Y, Makino T, Uzawa A, Kuwabara S.
    • Journal Title

      Mult Scler.

      Volume: 20 Issue: 3 Pages: 331-337

    • DOI

      10.1177/1352458513495581

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuromyelitis optica: concept, immunology and treatment.2014

    • Author(s)
      Uzawa A, Mori M, Kuwabara S.
    • Journal Title

      J Clin Neurosci.

      Volume: 21 Issue: 1 Pages: 12-21

    • DOI

      10.1016/j.jocn.2012.12.022

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of interleukin-6 in the pathogenesis of neuromyelitis optica2013

    • Author(s)
      Uzawa A, Mori M, Kuwabara S
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 4 Issue: 2 Pages: 167-172

    • DOI

      10.1111/cen3.12024

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Upbeat nystagmus at caudal brainstem lesions in four cases with multiple sclerosis and its related disorders2013

    • Author(s)
      Uzawa A, Mori M, Masuda S, Muto M, Uchida T, Kuwabara S
    • Journal Title

      Clin Exp Neuroimmunol.

      Volume: 4 Issue: 2 Pages: 206-9

    • DOI

      10.1111/cen3.12013

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks.2013

    • Author(s)
      Uzawa A, Mori M, Sawai S, Masuda S, Muto M, Uchida T, Ito S, Nomura F, Kuwabara S.
    • Journal Title

      Clin Chim Acta.

      Volume: 421 Pages: 181-183

    • DOI

      10.1016/j.cca.2013.03.020

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-high mobility group box 1 monoclonal antibody ameliorates experimental autoimmune encephalomyelitis.2013

    • Author(s)
      Uzawa A, Mori M, Taniguchi J, Masuda S, Muto M, Kuwabara S.
    • Journal Title

      Clin Exp Immunol

      Volume: 172 Issue: 1 Pages: 37-43

    • DOI

      10.1111/cei.12036

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolated ocular flutter2013

    • Author(s)
      Nasu S, Uzawa A, Mori M, Kuwabara S
    • Journal Title

      Neurology

      Volume: 80 Issue: 9 Pages: 867-867

    • DOI

      10.1212/wnl.0b013e31828407a8

    • Related Report
      2013 Final Research Report
  • [Journal Article] CSF high-mobility group box 1 is associated with intrathecal inflammation and astrocytic damage in neuromyelitis optica.2013

    • Author(s)
      Uzawa A, Mori M, Masuda S, Muto M, Kuwabara S.
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: 84 Issue: 5 Pages: 517-522

    • DOI

      10.1136/jnnp-2012-304039

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Seasonality of multiple sclerosis and neuromyelitis optica exacerbations in Japan.2013

    • Author(s)
      Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara S.
    • Journal Title

      Mult Scler.

      Volume: 19 Issue: 3 Pages: 378-379

    • DOI

      10.1177/1352458512452332

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuromyelitis optica: concept, immunology and treatment2013

    • Author(s)
      Uzawa A, Mori M, Kuwabara S
    • Journal Title

      J Clin Neurosci

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] When is neuromyelitis optica diagnosed after disease onset?2012

    • Author(s)
      Uzawa A, Mori M, Muto M, Masuda S, Kuwabara S
    • Journal Title

      J Neurol

      Volume: (in press) Issue: 8 Pages: 1600-5

    • DOI

      10.1007/s00415-011-6384-3

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-N-methyl D-aspartate-type glutamate receptor antibody-positive limbic encephalitis in a patient with multiple sclerosis2012

    • Author(s)
      Uzawa A, Mori M, Takahashi Y, Ogawa Y, Uchiyama T, Kuwabara S
    • Journal Title

      Clin Neurol Neurosurg

      Volume: (in press) Issue: 4 Pages: 402-404

    • DOI

      10.1016/j.clineuro.2011.10.047

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Seroconversion of anti-aquaporin-4 antibody in NMO spectrum disorder : a case report2012

    • Author(s)
      Mori M, Kawaguchi N, Uzawa A, Nemoto Y, Masuda S, Kuwabara S
    • Journal Title

      J Neurol

      Volume: (in press) Issue: 5 Pages: 980-1

    • DOI

      10.1007/s00415-011-6288-2

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] エナラプリルはブラジキニンの上昇を介してEAEの重症度を抑制する2013

    • Author(s)
      鵜沢顕之、森雅裕、谷口順子、増田冴子、武藤真弓、内田智彦、枡田大生、桑原聡
    • Organizer
      第25回日本神経免疫学会学術集会
    • Place of Presentation
      山口
    • Related Report
      2013 Final Research Report
  • [Presentation] High-mobility group box 1could be a therapeutic target in neuromyelitis optica and multiple sclerosis2013

    • Author(s)
      Akiyuki Uzawa, Masahiro Mori, Junko Taniguchi, Saeko Masuda, Mayumi Muto, Tomohiko Uchida, Hiroki Masuda, Satoshi Kuwabara
    • Organizer
      The 6th Pan Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)
    • Place of Presentation
      JAPAN, KYOTO
    • Related Report
      2013 Final Research Report
  • [Presentation] 多発性硬化症・視神経脊髄炎に対する新規治療ターゲットとしてのHMGB1の可能性2013

    • Author(s)
      桑原聡、鵜沢顕之、森雅裕、谷口順子、増田冴子、武藤真弓、内田智彦
    • Organizer
      平成24年度免疫性神経疾患に関する調査研究班班会議
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 視神経脊髄炎の髄液HMGB1濃度は中枢神経内の炎症とアストロサイト障害と関連する2013

    • Author(s)
      鵜沢顕之,森雅裕,谷口順子,増田冴子,武藤真弓 ,内田智彦,枡田大生,桑原聡
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] High-mobility group box 1could be a therapeutic target in neuromyelitis optica and multiple sclerosis2013

    • Author(s)
      Akiyuki Uzawa
    • Organizer
      Pan Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) 2013
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Annual Research Report
  • [Presentation] 多発性硬化症・視神経脊髄炎に対する新規治療ターゲットとしてのHMGB1の可能性2013

    • Author(s)
      鵜沢顕之
    • Organizer
      神経免疫班会議
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 視神経脊髄炎の髄液HMGB1濃度は中枢神経内の炎症とアストロサイト障害と関連する2013

    • Author(s)
      鵜沢顕之
    • Organizer
      日本神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 抗HMGB1抗体は EAEの重症度を抑制する : 多発性硬化症に対する新規治療応用の可能性2012

    • Author(s)
      鵜沢顕之、森雅裕、谷口順子、増田冴子、武藤真弓、内田智彦、桑原聡
    • Organizer
      第24回日本神経免疫学会学術集会
    • Place of Presentation
      長野
    • Related Report
      2013 Final Research Report
  • [Presentation] Markedly elevated sICAM-1 and sVCAM-1 levels in neuromyelitis optica : correlations with blood-brain barrier disruption2012

    • Author(s)
      Akiyuki Uzawa, Masahiro Mori, Saeko Masuda, Satoshi Kuwabara
    • Organizer
      The 13th Asian Oceanian Congress of Neurology
    • Place of Presentation
      Australia
    • Related Report
      2013 Final Research Report
  • [Presentation] NMOの臨床経過-2006年版改定診断基準の有用性の検討-2012

    • Author(s)
      鵜沢顕之,森雅裕,増田冴子,武藤真弓 ,桑原聡
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Markedly elevated sICAM-1 and sVCAM-1 levels in neuromyelitis optica: correlations with blood-brain barrier disruption2012

    • Author(s)
      Akiyuki Uzawa
    • Organizer
      Asian Oceanian Congress of Neurology
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2012 Research-status Report
  • [Presentation] 抗HMGB1抗体はEAEの重症度を抑制する:多発性硬化症に対する新規治療応用の可能性2012

    • Author(s)
      鵜沢顕之
    • Organizer
      日本神経免疫学会学術集会
    • Place of Presentation
      軽井沢
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.m.chiba-u.ac.jp/class/neurol/kenkyu/achievement/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 千葉大学大学院医学研究院 神経内科学

    • URL

      http://www.m.chiba-u.ac.jp/class/neurol/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 千葉大学大学院医学研究院 神経内科学

    • URL

      http://www.m.chiba-u.ac.jp/class/neurol/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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