Elsevier

Kidney International

Volume 77, Issue 4, 2 February 2010, Pages 339-349
Kidney International

Original Article
Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome

https://doi.org/10.1038/ki.2009.472Get rights and content
Under an Elsevier user license
open archive

Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI. Their overall clinical outcome was unfavorable, as half died or developed end-stage renal disease after their first syndrome episode. Eight patients with CFI mutations carried at least one additional known genetic risk factor for aHUS, such as a mutation in MCP, CFH, C3 or CFB; a compound heterozygous second mutation in CFI; or mutations in both the MCP and CFH genes. Five patients exhibited homozygous deletion of the Factor H-related protein 1 (CFHR-1) gene. Ten patients with aHUS had one mutation in their CFI gene (Factor I-aHUS), resulting in a quantitative or functional Factor I deficiency. Patients with a complete deletion of the CFHR-1 gene had a significantly higher risk of a bad prognosis compared with those with one Factor I mutation as their unique vulnerability feature. Our results emphasize the necessity of genetic screening for all susceptibility factors in patients with aHUS.

Keywords

alternative pathway
complement
complement Factor I
hemolytic and uremic syndrome
thrombotic microangiopathy

Cited by (0)

All the authors declared no competing interests.

8

Current address: Novartis Institutes for Biomedical Research, Disease Area Oncology, Basel, Switzerland