大多数溶血性尿毒综合征(HUS)是由肠出血性大肠杆菌(EHEC)感染引起的。导致不受控制的补体激活的遗传缺陷与更严重的非典型HUS(aHUS)相关。非EHEC感染可以引发疾病,然而,尚未研究诱发此类感染的补体缺陷。我们描述了一个2个月大的患者,感染了不同的革兰氏阴性细菌物种,导致aHUS。血清分析显示补体激活动力学缓慢。在补体抑制剂玻连蛋白中发现了罕见的变体R229C。重组突变的玻连蛋白在体外显示出增强的补体抑制,并且可能是感染的诱发因素。我们的工作表明,aHUS的遗传变化不仅会导致不受控制的补体激活,还会增加对aHUS感染的脆弱性。
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.