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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 膠原病学 / 抗好中球細胞質抗体関連血管炎

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 Pages: R101
  • 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
• [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
  • Year and Date: 20131025-30
• [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
  • Total Pages: 77-86
  • Publisher: 羊土社