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Development a novel therapy targeting NETs formation for anti-neutrophil cytoplasmic antibody-associated vasculitis

Research Project

Project/Area Number 24659472
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HARIGAI Masayoshi  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (20238207)

Co-Investigator(Kenkyū-buntansha) NANKI Toshihiro  帝京大学, 医学部, 准教授 (00282749)
MIYASAKA Nobuyuki  東京医科歯科大学, 医学部, 非常勤講師 (30157622)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膠原病学 / 抗好中球細胞質抗体関連血管炎 / 関節リウマチ / NETS形成 / シトルリン化 / 自然免疫
Research Abstract

Objective: We investigated involvement of neutrophil extracellular traps (NETs) formation in pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and tried to develop a murine model of systemic vasculitis. Methods: We separated neutrophils from peripheral blood using a magnet beads-based negative selection method. Immunoglobulin G (IgG) fraction of Myeloperoxidase (MPO)-ANCA positive serum was prepared using Protein A column. A murine model of systemic vasculitis was explored using Candida albicans water-soluble fraction (CAWS) and house-made rabbit anti-mouse MPO polyclonal antibody. Results. IgG fraction of MPO-ANCA positive serum induced NETs formation in the presence of recombinant C5a. CAWS and house-made rabbit anti-mouse MPO polyclonal antibody could not induce systemic vasculitis in C57BL6 mice. We measured panel of cytokines and chemokines in sera from patients with ANCA-associated vasculitis. All cytokines and chemokines were measurable in them.

Report

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

    (11 results)

All 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (4 results) Book (3 results)

  • [Journal Article] Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study2014

    • Author(s)
      Ken-ei Sada, Masahiro Yamamura, Masayoshi Harigai, et al.
    • Journal Title

      Arthritis Research & Therapy

      Volume: 16

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study2014

    • Author(s)
      1. Sada KE, Yamamura M, Harigai M, Fujii T, Dobashi H, Takasaki Y, Ito S, Yamada H, Wada T, Hirahashi J, Arimura Y, Makino H.
    • Journal Title

      Arthritis Res Ther

      Volume: 16 Issue: 2

    • DOI

      10.1186/ar4550

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of IRF5 polymorphism with MPO-ANCA positive vasculitis in a Japanese population2013

    • Author(s)
      Kawasaki A, Inoue N, Ajimi C, Sada K, Kobayashi S,Yamada H, Furukawa H, Sumida T, Tohma S, Miyasaka N, Matsuo S, Ozaki S, Hashimoto H, Makino H, Harigai M, Tsuchiya N.
    • Journal Title

      Genes Immun

      Volume: 14(8) Pages: 527-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 抗好中球細胞質抗体関連血管炎・急速進行性糸球体腎炎の寛解導入治療の現状とその有効性と安全性に関する観察研究(RemIT-JAV-RPGN)2013

    • Author(s)
      針谷正祥、山縣邦弘、本間栄、臼井丈一、土橋浩章、佐田憲英
    • Journal Title

      日本臨床「血管炎」増刊号

      Volume: 71 Pages: 381-385

    • Related Report
      2012 Research-status Report
  • [Presentation] High Clinical Remission Rate With Relatively High Incidence Of Serious Infection In Newly-Onset ANCA - Associated Vasculitides In Japan - A Report From The Nationwide Prospective Cohort Study2013

    • Author(s)
      Harigai Masayoshi, et al.
    • Organizer
      ACR/ARHP Annual Meeting
    • Place of Presentation
      San Diego
    • Related Report
      2013 Final Research Report
  • [Presentation] 4) High Clinical Remission Rate With Relatively High Incidence Of Serious Infection In Newly-Onset ANCA - Associated Vasculitides In Japan - A Report From The Nationwide Pro-spective Cohort Study2013

    • Author(s)
      Harigai Masayoshi, Sada Ken-ei, Fujii, Takao, Yamamura Masahiro, Arimura, Yoshihiro, and Makino Hi-rofumi.
    • Organizer
      ACR/ARHP Annual Meeting
    • Place of Presentation
      San Diego Convention Center USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2) わが国のANCA関連血管炎の前向きコホート研究RemIT-JAVにおける有効性に関する解析2013

    • Author(s)
      佐田憲映,山村昌弘,藤井隆夫,針谷正祥,有村義宏,槇野博史
    • Organizer
      第57回日本リウマチ学会総会・学術集会
    • Place of Presentation
      国立京都国際会館 京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 3) 抗好中球細胞質抗体関連血管炎の前向きコホート研究RemIT-JAVにおける治療開始後6ヶ月間の重篤感染症解析2013

    • Author(s)
      渡部香織,針谷正祥,佐田憲映,山村昌弘,藤井隆夫,有村義宏,槇野博史
    • Organizer
      第57回日本リウマチ学会総会・学術集会
    • Place of Presentation
      国立京都国際会館 京都市
    • Related Report
      2013 Annual Research Report
  • [Book] 免疫・アレルギー疾患イラストレイテッド基礎編免疫のしくみサイトカイン2013

    • Author(s)
      針谷正祥
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] 今日の処方(改訂第5版)2013

    • Author(s)
      針谷正祥
    • Total Pages
      1198
    • Publisher
      南江堂
    • Related Report
      2013 Annual Research Report
  • [Book] 免疫・アレルギー疾患イラストレイテッド2013

    • Author(s)
      針谷正祥:
    • Total Pages
      358
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report

URL: 

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

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