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

• Project/Area Number: 24659472
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Tokyo 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: ¥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.

Research Products

• [Journal Article] Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study (2014)
  • Author(s): Ken-ei Sada, Masahiro Yamamura, Masayoshi Harigai, et al.
  • Journal Title: Arthritis Research & Therapy Volume: 16
  • Peer Reviewed
• [Journal Article] Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study (2014)
  • 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
  • Peer Reviewed
• [Journal Article] Association of IRF5 polymorphism with MPO-ANCA positive vasculitis in a Japanese population (2013)
  • 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
  • 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
• [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 Study (2013)
  • Author(s): Harigai Masayoshi, et al.
  • Organizer: ACR/ARHP Annual Meeting
  • Place of Presentation: San Diego
• [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 Study (2013)
  • 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
• [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
• [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
• [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
• [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
• [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