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Sökning: WFRF:(Otten Marielle A.) > (2010) > Successful treatmen...

  • Yang, RuiRenal Division, Department of Medicine, Peking University First Hospital, Beijing, China (författare)

Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes

  • Artikel/kapitelEngelska2010

Förlag, utgivningsår, omfång ...

  • 2010-03-10
  • Oxford, UK :Oxford University Press (OUP),2010

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:8f9e3e12-7f96-43fd-a1ec-d136d0ecc08a
  • https://lup.lub.lu.se/record/1672285URI
  • https://doi.org/10.1093/ndt/gfq115DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-101578URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Otten, Marielle A.Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands (författare)
  • Hellmark, ThomasLund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Autoimmunitet och njursjukdomar,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Autoimmunity and kidney diseases,Lund University Research Groups,Division of Nephrology, Lund University and Lund University Hospital, Lund, Sweden(Swepub:lu)njur-the (författare)
  • Collin, MattiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Infection Medicine, Department of Clinical Sciences, Lund University and Lund University Hospital, Lund, Sweden(Swepub:lu)medk-mco (författare)
  • Björck, LarsLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Infection Medicine, Department of Clinical Sciences, Lund University and Lund University Hospital, Lund, Sweden(Swepub:lu)medk-lbj (författare)
  • Zhao, Ming-HuiRenal Division, Department of Medicine, Peking University First Hospital, Beijing, China (författare)
  • Daha, Mohamed R.Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands (författare)
  • Segelmark, MårtenLund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Nephrology, Lund University and Lund University Hospital, Lund, Sweden(Swepub:liu)marse71 (författare)
  • Renal Division, Department of Medicine, Peking University First Hospital, Beijing, ChinaDepartment of Nephrology, Leiden University Medical Center, Leiden, The Netherlands (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Nephrology Dialysis TransplantationOxford, UK : Oxford University Press (OUP)25:8, s. 2479-24861460-23850931-0509

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