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

Lambertus van den Heuvel; Kristian Riesbeck; Omaima El Tahir; Valentina Gracchi; Mariann Kremlitzka; Servaas A. Morre; A. Marceline van Furth; Birendra Singh; Marcin Okroj; Nicole van de Kar; Anna M. Blom; Elena Volokhina

doi:10.1038/s10038-017-0356-0

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

Lambertus van den Heuvel, Kristian Riesbeck, Omaima El Tahir, Valentina Gracchi, Mariann Kremlitzka, Servaas A. Morre, A. Marceline van Furth, Birendra Singh, Marcin Okroj, Nicole van de Kar, Anna M. Blom, Elena Volokhina^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.

Original language	English
Pages (from-to)	93-96
Number of pages	4
Journal	Journal of human genetics
Volume	63
Issue number	1
DOIs	https://doi.org/10.1038/s10038-017-0356-0
Publication status	Published - Jan-2018

Keywords

BORDETELLA-PERTUSSIS INFECTION

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title = "Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome",

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 indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.",

keywords = "BORDETELLA-PERTUSSIS INFECTION",

author = "{van den Heuvel}, Lambertus and Kristian Riesbeck and {El Tahir}, Omaima and Valentina Gracchi and Mariann Kremlitzka and Morre, {Servaas A.} and {van Furth}, {A. Marceline} and Birendra Singh and Marcin Okroj and {van de Kar}, Nicole and Blom, {Anna M.} and Elena Volokhina",

year = "2018",

month = jan,

doi = "10.1038/s10038-017-0356-0",

language = "English",

volume = "63",

pages = "93--96",

journal = "Journal of human genetics",

issn = "1434-5161",

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TY - JOUR

T1 - Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome

AU - van den Heuvel, Lambertus

AU - Riesbeck, Kristian

AU - El Tahir, Omaima

AU - Gracchi, Valentina

AU - Kremlitzka, Mariann

AU - Morre, Servaas A.

AU - van Furth, A. Marceline

AU - Singh, Birendra

AU - Okroj, Marcin

AU - van de Kar, Nicole

AU - Blom, Anna M.

AU - Volokhina, Elena

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - BORDETELLA-PERTUSSIS INFECTION

U2 - 10.1038/s10038-017-0356-0

DO - 10.1038/s10038-017-0356-0

M3 - Article

SN - 1434-5161

VL - 63

SP - 93

EP - 96

JO - Journal of human genetics

JF - Journal of human genetics

IS - 1

ER -

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

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Keywords

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