Schalk Gesa, Kirschfink Michael, Wehling Cyrill, Gastoldi Sara, Bergmann Carsten, Hoppe Bernd, Weber Lutz T
Pediatric Nephrology, Children's Hospital, University of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany,
Pediatr Nephrol. 2015 Jun;30(6):1039-42. doi: 10.1007/s00467-015-3078-6. Epub 2015 Mar 10.
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9).
CASE-DIAGNOSIS/TREATMENT: We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses.
Not every patient with aHUS and uncontrolled complement activation shows optimal therapeutic response to eculizumab with the recommended or even increased dosing regimen. Reliable outcome measures to determine the efficacy of treatment have to be defined.
非典型溶血尿毒综合征（aHUS）是血栓性微血管病的一种形式，其特征是替代补体途径不受控制地激活，随后生成末端补体复合物。死亡率会增加，尤其是在疾病的第一年。治疗选择包括血浆疗法以及使用抗C5单克隆抗体依库珠单抗进行末端补体阻断。依库珠单抗可防止补体级联反应的末端序列激活以及潜在溶解性末端补体复合物（C5b-9）的形成。
病例诊断/治疗：我们报告了一名3岁男孩，患有aHUS，原因是一种新的杂合性截短补体因子H突变，同时伴有其他已知与aHUS风险增加相关的变化。尽管接受了依库珠单抗治疗以及对经典和替代补体途径的最大程度抑制，但C3d和sC5b-9仍持续升高，且该患者出现多次复发。
并非每个患有aHUS且补体激活不受控制的患者对依库珠单抗采用推荐剂量甚至增加剂量方案都能表现出最佳治疗反应。必须确定用于确定治疗效果的可靠结局指标。
