Format

Send to

Choose Destination
Eur J Immunol. 2018 May;48(5):791-802. doi: 10.1002/eji.201747240. Epub 2018 Feb 22.

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

Author information

1
Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
2
Centre for Complement & Inflammation Research, Imperial College, UK.
3
Department of Anesthesia, University of Colorado School of Medicine, Aurora, CO, USA.
4
Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury.

KEYWORDS:

Complement; Factor H; IgM; Ischemia; Kidney

PMID:
29389016
PMCID:
PMC5992014
[Available on 2019-05-01]
DOI:
10.1002/eji.201747240
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center