THE MECHANISM OF NEPHRITOGENIC ANTI-DNA ANTIBODY PRODUCTION IN LUPUS NEPHRITIS

狼疮性肾炎肾源性抗DNA抗体产生机制

基本信息

  • 批准号:
    17591026
  • 负责人:
  • 金额:
    $ 1.34万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

The aim of the present study is to elucidate the antigenic trigger for the production of human nephritogenic anti-DNA antibodies. We found that a human monoclonal nephritogenic O-81 anti-DNA antibody bound to an endoplasmic reticulum stress-inducible protein, Herp.1. The anti-DNA or anti-Herp antibodies were obtained from the patients with active lupus nephritis by using a DNA-immobilized or a Herp-immobilized agarose, respectively. Lupus anti-DNA antibodies bound to Herp. Moreover, the anti-Herp antibodies showed specific binding to DNA.2. Each 6-week-old BALB/c female mouse was immunized intraperitoneally with Herp or Hen Egg Lysozyme (HEL). immunization with Herp, but not HEL, elicited anti-dsDNA as well as anti-ssDNA antibodies in BALB/c mice and formed the deposits of IgG in the renal glomeruli.3. The PBLs from SLE patients or healthy subjects were stained with a monoclonal anti-Herp antibody. Herp was spontaneously expressed in the PBLs of patients with active SLE, but in the PBLs of healthy subjects. The expression of Herp in the SLE PBLs was observed during the 72 hours in vitro culture without any stimulation. No expression of Herp was observed in healthy PBLs.4. To assess the antigenicity of Herp, the PBLs were cultured with Herp for 6 days, and the number of anti-DNA antibody producing clones was measured by ELISPOT assay. The number of anti-DNA antibody producing clones in the PBLs from active SLE patients increased in vitro after stimulation with Herp, but not with HEL or dsDNA. The PBLs form inactive SLE patients or healthy subjects did not respond to the stimulation with Herp.These results imply that an inducible intracellular self protein could be a trigger for human nephritogenic anti-DNA autoantibodies, where ER stress may be noted.
本研究的目的是阐明人致肾炎性抗DNA抗体产生的抗原触发因素。我们发现,人单克隆致肾炎O-81抗DNA抗体结合到内质网应激诱导蛋白,Herp.1。分别用DNA固定化琼脂糖和Herp固定化琼脂糖从活动性狼疮肾炎患者中获得抗DNA和抗Herp抗体。狼疮抗DNA抗体与疱疹病毒结合。此外,抗Herp抗体显示与DNA的特异性结合。每只6周龄的BALB/c雌性小鼠经腹腔注射Herp或Hen Egg Lysozyme(HEL)进行免疫。HEL免疫BALB/c小鼠后,可诱导抗dsDNA和抗ssDNA抗体产生,并在肾小球内形成IgG沉积. SLE患者和健康人的外周血淋巴细胞用抗Herp单克隆抗体染色。活动期SLE患者外周血淋巴细胞自发表达Herp,而健康人外周血淋巴细胞自发表达Herp。在无任何刺激的条件下,体外培养72小时,观察SLE PBLs中Herp的表达。在健康PBL中没有观察到Herp的表达。为了评估Herp的抗原性,将PBL与Herp一起培养6天,并通过ELISPOT测定来测量产生抗DNA抗体的克隆的数目。在体外用Herp刺激后,活动期SLE患者的PBL中产生抗DNA抗体的克隆数增加,但用HEL或dsDNA刺激后没有增加。SLE患者和健康人的PBL对Herp刺激无反应,提示细胞内可诱导的自身蛋白可能是诱发人肾源性抗DNA自身抗体的触发因子,其中可能存在ER应激。

项目成果

期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The role of endoplasmic reticulum protein in anti-DNA antibody production
内质网蛋白在抗DNA抗体产生中的作用
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sugihara;M;Tsutsumi;A;Suzuki;E;Wakamatsu;E;Suzuki;T;Ogishima;H;Hayashi;T;Chino;Y;Ishii;W;Mamura;M;Goto;D;Matsumoto;I;Ito;S;Sumida;T.;Suzuki E et al.;Yasuhiko Hirabayashi
  • 通讯作者:
    Yasuhiko Hirabayashi
A potential trigger of nephritogenic anti-DNA antibodies inlupus nephritis
狼疮性肾炎中肾炎性抗 DNA 抗体的潜在触发因素
Q fever with clinical features resembling systemic lupus erythematosus
  • DOI:
    10.2169/internalmedicine.45.1382
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
    1.2
  • 作者:
    Ohguchi, Hiroto;Hirabayashi, Yasuhiko;Sasaki, Takeshi
  • 通讯作者:
    Sasaki, Takeshi
自己抗体と細胞ストレス:抗DNA抗体産生における小胞体ストレス応答性蛋白の役割
自身抗体和细胞应激:内质网应激反应蛋白在抗 DNA 抗体产生中的作用
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nakagawa M;Hosokawa Y;Yonezumi M;Izumiyama K;Suzuki R;Tsuzuki S;Asaka M;Seto M;平林泰彦
  • 通讯作者:
    平林泰彦
The role of cell stress in systemic autoimmune disease
细胞应激在系统性自身免疫性疾病中的作用
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Suzuki E;ほか;Hiroshi Ohguchi;Suzuki E et al.;Yasuhiko Hirabayashi
  • 通讯作者:
    Yasuhiko Hirabayashi
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

HIRABAYASHI Yasuhiko其他文献

HIRABAYASHI Yasuhiko的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('HIRABAYASHI Yasuhiko', 18)}}的其他基金

Anti-endothelial cell antibody and thrombosis
抗内皮细胞抗体与血栓形成
  • 批准号:
    13670444
  • 财政年份:
    2001
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似国自然基金

Regulator of Lupus Nephritis 在狼疮性肾炎中的作用及其机制的研究
  • 批准号:
    81970599
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目

相似海外基金

Autoimmunity-Associated B Cells in Lupus Nephritis
狼疮性肾炎中自身免疫相关的 B 细胞
  • 批准号:
    10582053
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Clinical applications of urine proteomics to lupus nephritis
尿液蛋白质组学在狼疮性肾炎中的临床应用
  • 批准号:
    10567630
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Glycan biomarker panels in liquid biopsies for predicting treatment response in lupus nephritis
液体活检中的聚糖生物标志物组用于预测狼疮性肾炎的治疗反应
  • 批准号:
    10601270
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Treatment of lupus nephritis with nanoparticles that selectively target kidney glomeruli
用选择性靶向肾小球的纳米颗粒治疗狼疮性肾炎
  • 批准号:
    10679184
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Identifying autoimmune associated genes in patrolling monocytes that promote lupus nephritis
识别巡逻单核细胞中促进狼疮肾炎的自身免疫相关基因
  • 批准号:
    10726991
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Towards the Discovery of Predictive Biomarkers for Outcomes in Lupus Nephritis
致力于发现狼疮性肾炎预后的预测生物标志物
  • 批准号:
    491017
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Fellowship Programs
Early Access to Kidney Transplantation among Patients with Lupus Nephritis
狼疮性肾炎患者早期接受肾移植
  • 批准号:
    10679787
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Diagnostic utility of antibodies to post-translationally modified nucleosomes in lupus nephritis
翻译后修饰核小体抗体在狼疮性肾炎中的诊断效用
  • 批准号:
    10683684
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Integrin-Targeted Novel Oral Therapeutics for Lupus Nephritis
整合素靶向狼疮性肾炎新型口服疗法
  • 批准号:
    10760773
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
Objective Classification of Lupus Nephritis
狼疮性肾炎的客观分类
  • 批准号:
    10683624
  • 财政年份:
    2023
  • 资助金额:
    $ 1.34万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了