Departments of Pediatric Nephrology, and.
Departments of Pediatric Nephrology, andDepartment of Pediatric Nephrology, Emma Children's Hospital-Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands;
Pediatrics. 2014 Jun;133(6):e1764-8. doi: 10.1542/peds.2013-1594.
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening multisystemic condition often leading to end-stage renal failure. It results from an increased activation of the alternative pathway of the complement system due to mutations of genes coding for inhibitors of this pathway or from autoantibodies directed against them. Eculizumab is a monoclonal antibody directed against complement component C5 and inhibiting the activation of the effector limb of the complement system. Its efficacy has already been demonstrated in aHUS. The present article reports for the first time the use of eculizumab in a patient presenting with aHUS associated with circulating anti-complement Factor H autoantibodies and complicated by cardiac and neurologic symptoms. Our observation highlights the efficacy of eculizumab in this form of aHUS not only on renal symptoms but also on the extrarenal symptoms. It also suggests that eculizumab should be used very promptly after aHUS presentation to prevent life-threatening complications and to reduce the risk of chronic disabilities. To obtain a complete inhibition of the effector limb activation, the advised dosage must be respected. After this initial therapy in the autoimmune aHUS form, a long-term immunosuppressive treatment should be considered, to prevent relapses by reducing anti-complement Factor H autoantibody plasma levels.
非典型溶血尿毒综合征(aHUS)是一种危及生命的多系统疾病,常导致终末期肾衰竭。它是由于补体系统替代途径的激活增加引起的,这是由于编码该途径抑制剂的基因突变或针对这些抑制剂的自身抗体所致。依库珠单抗是一种针对补体成分 C5 的单克隆抗体,可抑制补体系统效应末端的激活。其疗效已在 aHUS 中得到证实。本文首次报道了依库珠单抗在伴有循环抗补体因子 H 自身抗体的 aHUS 患者中的应用,该患者合并心脏和神经系统症状。我们的观察结果强调了依库珠单抗在这种形式的 aHUS 中的疗效,不仅对肾脏症状有效,而且对肾外症状也有效。这也表明,依库珠单抗应该在 aHUS 出现后立即使用,以预防危及生命的并发症并降低慢性残疾的风险。为了获得对效应末端激活的完全抑制,必须遵守建议的剂量。在这种自身免疫性 aHUS 形式的初始治疗后,应考虑长期免疫抑制治疗,以通过降低抗补体因子 H 自身抗体的血浆水平来预防复发。