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

开发针对抗中性粒细胞胞质抗体相关性血管炎的 NET 形成的新疗法

• 批准号: 24659472
• 负责人: HARIGAI Masayoshi
• 金额: $ 2.33万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659472/
• 关键词: 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

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.

目的：我们研究了中性粒细胞胞外陷阱（NETs）的形成参与抗中性粒细胞胞浆抗体（ANCA）相关性血管炎的发病机制，并试图建立一个小鼠模型的系统性血管炎。方法：采用磁珠阴性选择法分离外周血中性粒细胞。用Protein A柱制备髓过氧化物酶（MPO）-ANCA阳性血清的免疫球蛋白G（IgG）组分。应用白念珠菌水溶性组分（CAWS）和自制兔抗小鼠髓过氧化物酶（MPO）多克隆抗体建立小鼠系统性血管炎模型。结果在重组C5 a存在下，MPO-ANCA阳性血清的IgG部分诱导NET形成。CAWS和自制兔抗鼠MPO多克隆抗体均不能诱导C57 BL 6小鼠发生系统性血管炎。我们检测了ANCA相关性血管炎患者血清中的细胞因子和趋化因子。所有细胞因子和趋化因子在它们中是可测量的。

项目成果

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

日本新发 ANCA 相关血管炎的临床缓解率较高，严重感染发生率相对较高 - 来自全国前瞻性队列研究的报告

• 发表时间: 2013
• 作者: Harigai Masayoshi;et al.
• 通讯作者: et al.

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)

抗中性粒细胞胞浆抗体相关性血管炎/急进性肾小球肾炎缓解诱导治疗现状及其疗效和安全性观察研究（RemIT-JAV-RPGN）

• 发表时间: 2013
• 期刊: 日本臨床「血管炎」増刊号
• 作者: 針谷正祥;山縣邦弘;本間栄;臼井丈一;土橋浩章;佐田憲英
• 通讯作者: 佐田憲英

免疫・アレルギー疾患イラストレイテッド

免疫学/过敏性疾病图解

• 发表时间: 2013
• 作者: 平原潔;中山俊憲
• 通讯作者: 中山俊憲

Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.

• DOI: 10.1186/ar4550
• 发表时间: 2014-04-23
• 期刊: Arthritis research & therapy
• 影响因子: 4.9
• 作者: Sada KE;Yamamura M;Harigai M;Fujii T;Dobashi H;Takasaki Y;Ito S;Yamada H;Wada T;Hirahashi J;Arimura Y;Makino H;Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan
• 通讯作者: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan

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

免疫学/过敏性疾病阐明免疫细胞因子的基础机制

• 发表时间: 2013
• 作者: Onishi A;Sugiyama D;Kumagai S;Morinobu A.;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;針谷正祥
• 通讯作者: 針谷正祥