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

Lindsey Goetz, Jennifer Laskowski, Brandon Renner, Matthew C. Pickering, Liudmila Kulik, Jelena Klawitter, Erik Stites, Uwe Christians, Johan van der Vlag, Kameswaran Ravichandran, V. Michael Holers, Joshua M. Thurman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)791-802
Number of pages12
JournalEuropean Journal of Immunology
Volume48
Issue number5
DOIs
StatePublished - May 2018
Externally publishedYes

Keywords

  • Complement
  • Factor H
  • IgM
  • Ischemia
  • Kidney

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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