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.
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Acknowledgments
This work was supported by the grants from the Dutch Kidney Foundation (13OI116, KFB 11.007, IP 10.22), ERA-EDTA (ERA STF 138–2013, ERA LTF 203–2014), and ESPN (2014.03) to E.V. and L.v.d.H. K.R. was supported by Swedish Medical Research Council (grant number K2015-57X-03163-43-4, www.vr.se) and Skåne County Council’s research and development foundation. M.O. is supported by National Science Centre Poland, grants 2015/18/M/NZ6/00334 and 2014/14/E/NZ6/00182.
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Dr. N.C.A.J. van de Kar is a member of the international advisory board of Alexion. The remaining authors declare no conflict of interest.
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van den Heuvel, L., Riesbeck, K., El Tahir, O. et al. Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome. J Hum Genet 63, 93–96 (2018). https://doi.org/10.1038/s10038-017-0356-0
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DOI: https://doi.org/10.1038/s10038-017-0356-0
