| Literature DB >> 29215086 |
Lambertus van den Heuvel1,2,3, Kristian Riesbeck4, Omaima El Tahir5,6, Valentina Gracchi7, Mariann Kremlitzka8, Servaas A Morré5,9, A Marceline van Furth6, Birendra Singh4, Marcin Okrój10, Nicole van de Kar1, Anna M Blom8, Elena Volokhina11,12.
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.Entities:
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Year: 2017 PMID： 29215086 DOI： 10.1038/s10038-017-0356-0
Source DB: PubMed Journal: J Hum Genet ISSN： 1434-5161 Impact factor: 3.172