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Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome

Van Den Heuvel, Lambertus; Riesbeck, Kristian LU ; El Tahir, Omaima; Gracchi, Valentina; Kremlitzka, Mariann LU ; Morré, Servaas A.; Van Furth, A. Marceline; Singh, Birendra LU ; Okrój, Marcin LU and Van De Kar, Nicole, et al. (2018) In Journal of Human Genetics 63(1). p.93-96
Abstract

Most cases of hemolytic uremic syndrome (HUS) are caused by infection with enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled complement activation are associated with the more severe atypical HUS (aHUS). Non-EHEC infections can trigger the disease, however, complement defects predisposing to such infections have not yet been studied. We describe a 2-month-old patient infected with different Gram-negative bacterial species resulting in aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant R229C was found in complement inhibitor vitronectin. Recombinant mutated vitronectin showed enhanced complement inhibition in vitro and may have been a predisposing factor for infection. Our work... (More)

Most cases of hemolytic uremic syndrome (HUS) are caused by infection with enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled complement activation are associated with the more severe atypical HUS (aHUS). Non-EHEC infections can trigger the disease, however, complement defects predisposing to such infections have not yet been studied. We describe a 2-month-old patient infected with different Gram-negative bacterial species resulting in aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant R229C was found in complement inhibitor vitronectin. Recombinant mutated vitronectin showed enhanced complement inhibition in vitro and may have been a predisposing factor for infection. Our work indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.

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publication status
published
subject
keywords
genetic predisposition, Infection, Hemolytic uremic syndrome
in
Journal of Human Genetics
volume
63
issue
1
pages
4 pages
publisher
Springer
external identifiers
  • scopus:85040330480
ISSN
1434-5161
DOI
10.1038/s10038-017-0356-0
language
English
LU publication?
yes
id
42455dd8-cff4-45e8-acd8-a412e9de1778
date added to LUP
2018-02-05 10:10:15
date last changed
2018-02-13 07:18:18
@article{42455dd8-cff4-45e8-acd8-a412e9de1778,
  abstract     = {<p>Most cases of hemolytic uremic syndrome (HUS) are caused by infection with enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled complement activation are associated with the more severe atypical HUS (aHUS). Non-EHEC infections can trigger the disease, however, complement defects predisposing to such infections have not yet been studied. We describe a 2-month-old patient infected with different Gram-negative bacterial species resulting in aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant R229C was found in complement inhibitor vitronectin. Recombinant mutated vitronectin showed enhanced complement inhibition in vitro and may have been a predisposing factor for infection. Our work indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.</p>},
  author       = {Van Den Heuvel, Lambertus and Riesbeck, Kristian and El Tahir, Omaima and Gracchi, Valentina and Kremlitzka, Mariann and Morré, Servaas A. and Van Furth, A. Marceline and Singh, Birendra and Okrój, Marcin and Van De Kar, Nicole and Blom, Anna M. and Volokhina, Elena},
  issn         = {1434-5161},
  keyword      = {genetic predisposition,Infection,Hemolytic uremic syndrome},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {93--96},
  publisher    = {Springer},
  series       = {Journal of Human Genetics},
  title        = {Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome},
  url          = {http://dx.doi.org/10.1038/s10038-017-0356-0},
  volume       = {63},
  year         = {2018},
}