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

Bienaime, Frank ; Dragon-Durey, Marie-Agnes ; Regnier, Catherine H. ; Nilsson, Sara LU ; Kwan, Wing H. ; Blouin, Jacques ; Jablonski, Mathieu ; Renault, Nicolas ; Rameix-Welti, Marie-Anne and Loirat, Chantal , et al. (2010) In Kidney International 77(4). p.339-349
Abstract
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... (More)
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 (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hemolytic and, complement Factor I, alternative pathway, complement, uremic syndrome, thrombotic microangiopathy
in
Kidney International
volume
77
issue
4
pages
339 - 349
publisher
Nature Publishing Group
external identifiers
  • wos:000274051700011
  • scopus:75749153964
  • pmid:20016463
ISSN
1523-1755
DOI
10.1038/ki.2009.472
language
English
LU publication?
yes
id
352bff10-e4d6-4a75-a992-d4b4d658ac56 (old id 1546946)
date added to LUP
2016-04-01 14:17:46
date last changed
2025-04-04 14:00:54
@article{352bff10-e4d6-4a75-a992-d4b4d658ac56,
  abstract     = {{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}},
  author       = {{Bienaime, Frank and Dragon-Durey, Marie-Agnes and Regnier, Catherine H. and Nilsson, Sara and Kwan, Wing H. and Blouin, Jacques and Jablonski, Mathieu and Renault, Nicolas and Rameix-Welti, Marie-Anne and Loirat, Chantal and Sautes-Fridman, Catherine and Villoutreix, Bruno O. and Blom, Anna and Fremeaux-Bacchi, Veronique}},
  issn         = {{1523-1755}},
  keywords     = {{hemolytic and; complement Factor I; alternative pathway; complement; uremic syndrome; thrombotic microangiopathy}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{339--349}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Kidney International}},
  title        = {{Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome}},
  url          = {{http://dx.doi.org/10.1038/ki.2009.472}},
  doi          = {{10.1038/ki.2009.472}},
  volume       = {{77}},
  year         = {{2010}},
}