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Associated factors with cerebrospinal fluid cytokine levels in patients with neuropsychiatric systemic lupus erythematosus

Research Project

Project/Area Number 16K09901
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Takao Fujii  和歌山県立医科大学, 医学部, 教授 (70255462)

Research Collaborator Ishigooka Nozomi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords全身性エリテマトーデス / 抗核抗体 / サイトカイン / 中枢神経症状 / 自己抗体 / 脳脊髄液 / IL-6 / ケモカイン / 血液脳関門 / 中枢神経障害
Outline of Final Research Achievements

Autoantibodies (autoAbs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We examined combined effects of CSF anti-N-methyl D-aspartate receptor NR2 subunit (NR2) Ab and anti-U1RNP Ab on IMs in patients with NPSLE. CSF samples were collected from 69 patients with acute-phase NPSLE and 13 non-NPSLE controls. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. Elevated CSF IL-6 and IL-8 levels were mainly associated with anti-NR2 and U1RNP Ab positivity, respectively. CSF IL-6, IL-8 and MIG levels were higher in CSF anti-NR2 and anti-U1RNP Ab double positive group than in anti-NR2 Ab-positive alone group. Therefore, CSF anti-NR2 and anti-U1RNP Abs have combined effects on the elevation of CSF IL-6 and MIG levels in patients with NPSLE.

Academic Significance and Societal Importance of the Research Achievements

膠原病の代表的疾患である全身性エリテマトーデスではしばしば脳の炎症を引き起こし、生命予後に影響を与える。この病態(NPSLE)は極めて重症と考えられ、そりよい治療法の開発が望まれるが、世界的にもガイドラインが整備されているとは言いがたい。本研究で、NPSLE患者の症状と深く関連するとされる脳脊髄液(CSF)中の液性因子がいかなる自己抗体と関連するかを明確にした。専門施設においてCSFは比較的容易に採取できるため、その自己抗体の検査を行うことでいかなる液性因子をターゲットとして治療すればよいかについて示唆に富む結果が得られたため、近日中に論文発表する予定である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.2019

    • Author(s)
      Ishikawa Y, Hashimoto M, Ito H, Tanaka M, Yukawa N, Fujii T, Yamamoto W, Mimori T, Terao C.
    • Journal Title

      Seminars in Arthritis and Rheumatism

      Volume: (印刷中) Issue: 2 Pages: 204-210

    • DOI

      10.1016/j.semarthrit.2019.02.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膠原病における自己抗体の臨床的意義と病原性2019

    • Author(s)
      藤井 隆夫
    • Journal Title

      日本内科学会雑誌

      Volume: 108 Pages: 493-497

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis.2017

    • Author(s)
      Kuramoto N, Ohmura K, Ikari K, Yano K, Furu M, Yamakawa N, Hashimoto M, Ito H, Fujii T, Murakami K, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Taniguchi A, Momohara S, Yamanaka H, Matsuda F, Mimori T, Terao C
    • Journal Title

      Sc Rep

      Volume: 7 Issue: 1 Pages: 6911-6911

    • DOI

      10.1038/s41598-017-07137-4

    • NAID

      120006368159

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-carbamylated Protein Antibodies Are Detectable in Various Connective Tissue Diseases.2017

    • Author(s)
      Nakabo S, Yoshifuji H, Hashimoto M, Imura Y, Nakashima R, Murakami K, Kuramoto N, Ito S, Satoh J, Tanaka M, Fujii T, Mimori T, Ohmura K
    • Journal Title

      J Rheumatol

      Volume: 44 Pages: 1384-1388

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Carbamylated albumin is one of the target antigens of anti-carbamylated protein antibodies.2017

    • Author(s)
      Nakabo S, Hashimoto M, Ito S, Furu M, Ito H, Fujii T, Yoshifuji H, Imura Y, Nakashima R, Murakami K, Kuramoto N, Tanaka M, Satoh J, Ishigami A, Morita S, Mimori T, Ohmura K.
    • Journal Title

      Rheumatology (Oxford)

      Volume: in press Issue: 7 Pages: 1217-1226

    • DOI

      10.1093/rheumatology/kex088

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts2017

    • Author(s)
      Mori M, Hashimoto M, Matsuo T, Fujii T, Furu M, Ito H, Yoshitomi H, Hirose J, Ito Y, Akizuki S, Nakashima R, Imura Y, Yukawa N, Yoshifuji H, Ohmura K, Mimori T
    • Journal Title

      Mod Rheumatol

      Volume: 27 Issue: 3 Pages: 448-456

    • DOI

      10.1080/14397595.2016.1220353

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunogenicity and lupus-like autoantibody production can be linked to each other along with type I interferon production in patients with rheumatoid arthritis treated with infliximab: A retrospective study of a single center cohort2016

    • Author(s)
      Yuki Ishikawa, Takao Fujii, Seiko Kondo Ishikawa, Naoichiro Yukawa, Motomu Hashimoto, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, and Tsuneyo Mimori
    • Journal Title

      PLoS One

      Volume: 11 Issue: 9 Pages: e0162896-e0162896

    • DOI

      10.1371/journal.pone.0162896

    • NAID

      120005860037

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Indirect pathogenic roles of cerebrospinal fluid anti-U1RNP antibodies in the presence of anti-NR2 antibodies in patients with neuropsychiatric systemic lupus erythematosus.2018

    • Author(s)
      Fujii T, Kondo-Ishikawa S, Ishigooka N, Yoshifuji H, Ohmura K, Mimori T.
    • Organizer
      The Annual European Congress of Rheumatology EULAR 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 全身性エリテマトーデスの中枢神経症状と関連する自己抗体とその臨床的・病因的意義2017

    • Author(s)
      藤井 隆夫
    • Organizer
      第61回日本リウマチ学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 膠原病診療における自己抗体測定の臨床的意義と活用法2016

    • Author(s)
      藤井隆夫
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 精神神経ループスにおける脳脊髄液中の自己抗体とサイトカインとの相関2016

    • Author(s)
      近藤聖子、藤井隆夫、石郷岡望、橋本求、井村嘉孝、湯川尚一郎、吉藤元、大村浩一郎、三森経世
    • Organizer
      第113回日本内科学会総会・講演会
    • Place of Presentation
      東京
    • Year and Date
      2016-04-15
    • Related Report
      2016 Research-status Report
  • [Book] 内科外来診断navi2017

    • Author(s)
      藤井隆夫
    • Total Pages
      358
    • Publisher
      中外医学社
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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