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学科主题: 临床医学
题名:
Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes
作者: Yang, Rui5; Otten, Marielle A.4; Hellmark, Thomas1,2; Collin, Mattias2,3; Bjorck, Lars2,3; Zhao, Ming-Hui5; Daha, Mohamed R.4; Segelmark, Marten1,2
关键词: anti-GBM disease ; EndoS ; Goodpasture&prime ; s disease ; IdeS
刊名: NEPHROLOGY DIALYSIS TRANSPLANTATION
发表日期: 2010-08-01
DOI: 10.1093/ndt/gfq115
卷: 25, 期:8, 页:2479-2486
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Transplantation ; Urology & Nephrology
研究领域[WOS]: Transplantation ; Urology & Nephrology
关键词[WOS]: CYSTEINE PROTEINASE ; STRICT SPECIFICITY ; IN-VIVO ; PYOGENES ; DISEASE ; ENDOPEPTIDASE ; GLYCOSYLATION ; ANTIBODIES ; ARTHRITIS ; CLEAVAGE
英文摘要:

Background. Anti-glomerular basement membrane (anti-GBM) disease often results in end-stage renal failure despite therapy with plasma exchange and immunosuppressive drugs. The newly discovered streptococcal enzymes IgG-degrading enzyme of S.pyogenes (IdeS) and endoglycosidase S (EndoS) act with remarkable specificity on circulating IgG. In this study, we investigate their ability in vivo to prevent damage mediated by kidney-bound antibodies in a mouse model of anti-GBM disease.

Methods. Anti-GBM disease was induced in mice by injection of subnephritogenic doses of rabbit anti-mouse GBM, followed a week later by injection of monoclonal mouse anti-rabbit IgG antibodies. By administrating IdeS or EndoS as fusion partners with GST between these antibody injections, we tested their ability to prevent damage by acting on kidney-bound rabbit anti-GBM. Control animals received placebo injections.

Results. All animals in the positive control groups developed severe albuminuria immediately after the second antibody injection (mean, 2.51 mg/24 h; range, 0.13-8.20). This was significantly diminished by EndoS (1.3 +/- 1.3 mg/24 h) and completely prevented by IdeS (0.017 +/- 0.014 mg/24 h). Immunofluorescence studies showed that IdeS treatment effectively removed the Fc fragments of the rabbit IgG. This was accompanied by a significant reduction of the deposition of the complement components C3 and C1q, and this diminished the recruitment of leukocytes to the glomeruli.

Conclusion. IdeS degrades IgG bound to the GBM in vivo, thereby preventing renal damage in this animal model. Most likely, IdeS would degrade both circulating and kidney-bound anti-GBM in patients with Goodpasture′s disease. Whether this would lead to a halt in disease progression and a better prognosis remains to be determined.

语种: 英语
所属项目编号: 2007-3520 ; 2005-4791
项目资助者: Swedish Research Council ; Foundation of Crafoord ; Swedish Society for Medicine ; Royal Physiografic Society ; King Gustaf V&prime ; s Memorial Fund ; Hansa Medical AB ; Foundation of Kock ; Foundation of Bergvall ; Foundation of Osterlund ; Foundation of Wiberg
WOS记录号: WOS:000281483300016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60465
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Lund Univ, Div Nephrol, Lund, Sweden
2.Univ Lund Hosp, S-22185 Lund, Sweden
3.Lund Univ, Dept Clin Sci, Div Infect Med, Lund, Sweden
4.Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands
5.Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100871, Peoples R China

Recommended Citation:
Yang, Rui,Otten, Marielle A.,Hellmark, Thomas,et al. Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes[J]. NEPHROLOGY DIALYSIS TRANSPLANTATION,2010,25(8):2479-2486.
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