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
AbstractMost 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.
|Journal series||Journal of Human Genetics, ISSN 1434-5161, (A 20 pkt)|
|Publication size in sheets||0.50|
|Score||= 20.0, 28-01-2020, ArticleFromJournal|
|Publication indicators||: 2018 = 1.043; : 2018 = 3.545 (2) - 2018=2.912 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.