| Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes. | |
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MedLine Citation:
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PMID: 20219834 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Rui Yang; Marielle A Otten; Thomas Hellmark; Mattias Collin; Lars Björck; Ming-Hui Zhao; Mohamed R Daha; Mårten Segelmark |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-10 |
Journal Detail:
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Title: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Volume: 25 ISSN: 1460-2385 ISO Abbreviation: Nephrol. Dial. Transplant. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-19 Completed Date: 2010-10-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: England |
Other Details:
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Languages: eng Pagination: 2479-86 Citation Subset: IM |
Affiliation:
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Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Glomerular Basement Membrane Disease / chemically induced, drug therapy*, pathology Autoantibodies / adverse effects Bacterial Proteins / therapeutic use* Disease Models, Animal Glycoside Hydrolases / therapeutic use* Immunoglobulin G / blood Kidney Glomerulus / pathology Male Mice Mice, Inbred C57BL Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Bacterial Proteins; 0/Immunoglobulin G; 0/Mac-1-like protein, Streptococcus; 0/antiglomerular basement membrane antibody; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.-/NDOS protein, Streptococcus pyogenes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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