• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of the mechanism of blood-brain barrier damages in NPSLE

Research Project

Project/Area Number 15K09556
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKitasato University

Principal Investigator

Hirohata Shunsei  北里大学, 医学部, 客員教授 (90189895)

Co-Investigator(Kenkyū-buntansha) 永井 立夫  北里大学, 医学部, 講師 (60365947)
小川 英佑  北里大学, 医学部, 助教 (30525423)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsNPSLE / acute confusional state / MRI / IL-6 / anti-Sm / C5a / 脳血液関門 / 自己抗体 / 抗Sm抗体 / 単球 / 中枢神経ループス / 補体第5成分 / ループス腎炎 / 脳MRI
Outline of Final Research Achievements

Acute confusional state (ACS) is the most recalcitrant manifestation in diffuse neuropsychiatric systemic lupus erythematosus (NPSLE). We have disclosed that the presence of brain MRI abnormalities, the presence of serum anti-Sm antibodies and serum IL-6 levels significantly increased the risk for mortality in multivariate analysis in a retrospective study of 36 patients with ACS.
The damage of blood brain barrier (BBB) has been found to be important in the development of ACS. We have disclosed that serum C5a was elevated in NPSLE, contributing to BBB damages. We have also revealed that serum IL-6 might play a most important role in BBB breakdown in NPSLE. Moreover, we have demonstrated that serum anti-Sm antibodies play a most important role in the disruption of BBB. Finally, it was demonstrated that anti-Sm synergistically enhanced the production of IL-6 by human monocytes in the presence of anti-RNP, suggesting that anti-Sm might damage BBB through such an inflammatory process.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 10 results,  Invited: 4 results) Book (4 results)

  • [Int'l Joint Research] The Feinstein Institute for Med Res/Hofstra Northwell Sch Med(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Hokkaido University(日本)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Serbia University Sch Med(Serbia)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Role of serum autoantibodies in blood brain barrier damages in neuropsychiatric systemic lupus erythematosus.2018

    • Author(s)
      Hirohata S, Sakuma Y, Matsueda Y, Arinuma Y, Yanagida T
    • Journal Title

      Clin Exp Rheumatol

      Volume: 36

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder: Do They Share Common Targets?2018

    • Author(s)
      Mader S, Jeganathan V, Arinuma Y, Fujieda Y, Dujmovic I, Drulovic J, Shimizu Y, Sakuma Y, Stern JNH, Aranow C, Mackay M, Yasuda S, Atsumi T, Hirohata S, Diamond B.
    • Journal Title

      Arthritis Rheumatology

      Volume: 70 Issue: 2 Pages: 277-286

    • DOI

      10.1002/art.40356

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Brain MRI in patients with acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus2017

    • Author(s)
      Abe G, Kikuchi H, Arinuma Y, Hirohata S.
    • Journal Title

      Mod Rheumatol

      Volume: 27 Issue: 2 Pages: 278

    • DOI

      10.1080/14397595.2016.1193966

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Differential activation mechanisms of serum C5a in lupus nephritis and neuropsychiatric systemic lupus erythematosus.2017

    • Author(s)
      Sakuma Y, Nagai T, Yoshio T, Hirohata S.
    • Journal Title

      Mod Rheumatol

      Volume: 27 Issue: 2 Pages: 292-297

    • DOI

      10.1080/14397595.2016.1193965

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.2016

    • Author(s)
      Yoshio T, Okamoto H, Kurasawa K, Dei Y, Hirohata S, Minota S.
    • Journal Title

      Lupus

      Volume: 25 Issue: 9 Pages: 997-1003

    • DOI

      10.1177/0961203316629556

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.2016

    • Author(s)
      Tjensvoll AB, Lauvsnes MB, Hirohata S, Beyer MK, Greve OJ, Kvivik I, Kvaloey JT, Harboe E, Goeransson LG, Omdal R.
    • Journal Title

      Eur J Neurol

      Volume: 23 Issue: 4 Pages: 780-786

    • DOI

      10.1111/ene.12946

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study2016

    • Author(s)
      Hibi T, Hirohata S, Kikuchi H, Tateishi U, Sato N, Ozaki K, Kondo K, Ishigatsubo Y.
    • Journal Title

      Medicine (Baltimore)

      Volume: 95 Issue: 24 Pages: e3863-e3863

    • DOI

      10.1097/md.0000000000003863

    • URL

      https://pure.teikyo.jp/en/publications/ceb18309-2031-4588-8df8-37644a8cfc64

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retrospective analysis of long-term outcome of chronic progressive neurological manifestations in Behcet's disease2015

    • Author(s)
      Hirohata S, Kikuchi H, Sawada T, Nagafuchi H, Kuwana M, Takeno M, Ishigatsubo Y.
    • Journal Title

      J Neurol Sci

      Volume: 349 Issue: 1-2 Pages: 143

    • DOI

      10.1016/j.jns.2015.01.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of anti-IL-6 receptor antibody on human monocytes.2015

    • Author(s)
      Tono T, Aihara S, Hoshiyama T, Arinuma Y, Nagai T, Hirohata S.
    • Journal Title

      Mod Rheumatol

      Volume: 25 Issue: 1 Pages: 79-84

    • DOI

      10.3109/14397595.2014.914016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors with neuropsychiatric systemic lupus erythematosus.2015

    • Author(s)
      Ogawa E, Nagai T, Sakuma Y, Arinuma Y, Hirohata S
    • Journal Title

      Mod Rheumatol

      Volume: 26 Issue: 3 Pages: 377-383

    • DOI

      10.3109/14397595.2015.1083163

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Role of serum interleukin-6 in blood brain barrier damages in neuropsychiatric systemic lupus erythematosus.2017

    • Author(s)
      Hirohata S, Marsueda Y, Yanagida T, Yoshio T
    • Organizer
      EULAR 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シンポジウム6 膠原病の難治性病態 6-2中枢神経ループス.2017

    • Author(s)
      廣畑 俊成, 松枝佑、有沼良幸
    • Organizer
      第32回日本臨床リウマチ学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Analysis of the influences of various factors on the prognosis of acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus.2016

    • Author(s)
      Abe G, Arinuma Y, Kikuchi H, Hirohata S
    • Organizer
      80th Annual Scientific Meeting, American College of Rheumatology
    • Place of Presentation
      Washington, DC (U.S.A.)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膠原病内科から学ぶ神経疾患.2016

    • Author(s)
      廣畑 俊成
    • Organizer
      第34回日本神経治療学会総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Role of autoantibodies in neuropsychiatric systemic lupus erythematosus.2016

    • Author(s)
      Hirohata S, Arinuma Y, Yanagida T, Yoshio T
    • Organizer
      The 13 th International Workshop on Autoantibodies and Autoimmunity
    • Place of Presentation
      The Westin Miyako Kyoto (Kyoto, Japan)
    • Year and Date
      2016-10-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Serum C5a is increased in lupus nephritis as well as in neuropsychiatric systemic lupus erythematosus through different mechanisms.2016

    • Author(s)
      Sakuma Y, Nagai T, Yoshio T, Hirohata S
    • Organizer
      EULAR 2016
    • Place of Presentation
      London (U.K.)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain MRI in patients with acute confusional state of diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus.2016

    • Author(s)
      Abe G, Arinuma Y, Sakuma Y, Kikuchi H, Hirohata S
    • Organizer
      EULAR 2016
    • Place of Presentation
      London (U.K.)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経精神ループスに対するミコフェノール酸モフェチルの有効性に関する検討.2016

    • Author(s)
      児玉 華子、小川 英佑、田中 住明、谷 名、田中 知樹、安部 学朗、工藤 雄大、和田 達彦、永井 立夫、廣畑 俊成
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] Role of serum autoantibodies in blood-brain barrier damages in neuropsychiatric systemic lupus erythematosus.2016

    • Author(s)
      Hirohata S,Sakuma Y, Yanagida T, Yoshio T
    • Organizer
      10th International Congress on Autoimmunity
    • Place of Presentation
      Leipzig (Germany)
    • Year and Date
      2016-04-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Association of Antibodies to the NR1 Subunit of N-Methyl-D-Aspartate Receptors with Neuropsychiatric Systemic Lupus Erythematosus.2015

    • Author(s)
      Ogawa E, Nagai T, Sakuma Y, Arinuma Y, Hirohata S.
    • Organizer
      79th Annual Scientific Meeting, American College of Rheumatology
    • Place of Presentation
      San Francisco (U.S.A.)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Upregulation of Complement C3 and Alpha-2-Macroglobulin in Cerebrospinal Fluid of Neuropsychiatric Systemic Lupus Erythematosus .2015

    • Author(s)
      Asano T, Sato S, Kobayashi H, Kariya Y, Ito H, Hoshi K, Yoshihara A, Ugawa Y, Takahashi M, Sekine H, Hirohata S, Watanabe H, Ohira H, Hashimoto Y.
    • Organizer
      79th Annual Scientific Meeting, American College of Rheumatology
    • Place of Presentation
      San Francisco (U.S.A.)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 自己免疫疾患の中枢神経病変.2015

    • Author(s)
      廣畑 俊成
    • Organizer
      第43回 日本臨床免疫学会総会
    • Place of Presentation
      神戸国際会議場 (兵庫県神戸市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Blood-brain barrier damages in the pathogenesis of acute confusional state in systemic lupus erythematosus.2015

    • Author(s)
      Hirohata S, Arinuma Y, Yanagida T, Yoshio T
    • Organizer
      LUPUS2015
    • Place of Presentation
      Vienna (Austria)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of cerebrospinal fluid anti-NR1 glutamate receptor antibodies in neuropsychiatric systemic lupus erythematosus.2015

    • Author(s)
      Ogawa E, Nagai T, Sakuma Y, Arinuma Y, Hirohata S
    • Organizer
      LUPUS2015
    • Place of Presentation
      Vienna (Austria)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Neuropsychiatric Systemic Lupus Erythematosus: Pathogenesis, Clinical Aspects and Treatment.2018

    • Author(s)
      Hirohata S
    • Total Pages
      189
    • Publisher
      Springer International Publishing AG
    • ISBN
      9783319764955
    • Related Report
      2017 Annual Research Report
  • [Book] リウマチ・膠原病アトラス2018

    • Author(s)
      廣畑俊成
    • Total Pages
      192
    • Publisher
      文光堂
    • ISBN
      9784830620454
    • Related Report
      2017 Annual Research Report
  • [Book] 最新医学 別冊 診断と治療のABC 118 全身性エリテマトーデス, (重要な病態の管理と治療 1.神経精神SLE).2016

    • Author(s)
      廣畑俊成
    • Total Pages
      10
    • Publisher
      最新医学社
    • Related Report
      2016 Research-status Report
  • [Book] リウマチ膠原病診療ガイド2016

    • Author(s)
      廣畑 俊成
    • Total Pages
      115
    • Publisher
      文光堂
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-06-07  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi