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. Morré , Marceline van Furth , Birendra Singh , Marcin Okrój , Nicole van De Kar , Anna Blom , Elena Volokhina


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.
Author Lambertus van Den Heuvel
Lambertus van Den Heuvel,,
, Kristian Riesbeck
Kristian Riesbeck,,
, Omaima El Tahir
Omaima El Tahir,,
, Valentina Gracchi
Valentina Gracchi,,
, Mariann Kremlitzka
Mariann Kremlitzka,,
, Servaas A. Morré
Servaas A. Morré,,
, Marceline van Furth
Marceline van Furth,,
, Birendra Singh
Birendra Singh,,
, Marcin Okrój (IFB/DMedB)
Marcin Okrój,,
- Department of Medical Biotechnology
, Nicole van De Kar
Nicole van De Kar,,
et al.`
Journal seriesJournal of Human Genetics, ISSN 1434-5161, (A 20 pkt)
Issue year2018
Publication size in sheets0.50
ASJC Classification2716 Genetics(clinical); 1311 Genetics
Languageen angielski
Score (nominal)20
Score sourcejournalList
ScoreMinisterial score = 20.0, 28-01-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.043; WoS Impact Factor: 2018 = 3.545 (2) - 2018=2.912 (5)
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