Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency.

Authors
  • Ruseva, Marieta M
  • Vernon, Katherine A
  • Lesher, Allison M
  • Schwaeble, Wilhelm J
  • Ali, Youssif M
  • Botto, Marina
  • Cook, Terence
  • Song, Wenchao
  • Stover, Cordula M
  • Pickering, Matthew Caleb
Type
Published Article
Journal
Journal of the American Society of Nephrology
Publisher
American Society of Nephrology
Publication Date
Jan 01, 2013
Volume
24
Issue
1
Pages
43–52
Identifiers
DOI: 10.1681/ASN.2012060571
PMID: 23184055
Source
Medline
License
Unknown

Abstract

Complement factor H (CFH) is a negative regulator of the alternative pathway of complement, and properdin is the sole positive regulator. CFH-deficient mice (CFH(-/-)) develop uncontrolled C3 activation and spontaneous renal disease characterized by accumulation of C3 along the glomerular basement membrane, but the role of properdin in the pathophysiology is unknown. Here, we studied mice deficient in both CFH and properdin (CFH(-/-).P(-/-)). Although CFH(-/-) mice had plasma depleted of both C3 and C5, CFH(-/-).P(-/-) animals exhibited depletion of C3 predominantly, recapitulating the plasma complement profile observed in humans with properdin-independent C3 nephritic factors. Glomerular inflammation, thickening of the capillary wall, and glomerular C3 staining were significantly increased in CFH(-/-).P(-/-) compared with CFH(-/-) mice. We previously reported that exogenous CFH ameliorates C3 staining of the glomerular basement membrane and triggers the appearance of mesangial C3 deposits in CFH(-/-) mice; here, we show that these effects require properdin. In summary, during uncontrolled activation of C3 driven by complete CFH deficiency, properdin influences the intraglomerular localization of C3, suggesting that therapeutic inhibition of properdin would be detrimental in this setting.

Report this publication

Statistics

Seen <100 times