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

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Author

  • Frank Bienaime
  • Marie-Agnes Dragon-Durey
  • Catherine H. Regnier
  • Sara Nilsson
  • Wing H. Kwan
  • Jacques Blouin
  • Mathieu Jablonski
  • Nicolas Renault
  • Marie-Anne Rameix-Welti
  • Chantal Loirat
  • Catherine Sautes-Fridman
  • Bruno O. Villoutreix
  • Anna Blom
  • Veronique Fremeaux-Bacchi
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Summary, in English

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. Kidney International (2010) 77, 339-349; doi: 10.1038/ki.2009.472; published online 16 December 2009

Publishing year

2010

Language

English

Pages

339-349

Publication/Series

Kidney International

Volume

77

Issue

4

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Urology and Nephrology

Keywords

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

Status

Published

Research group

  • Clinical Chemistry, Malmö
  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1523-1755