Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches
Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches
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DOI：
10.1055/s-0034-1376153
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发表时间：
2014-06-01
影响因子：
5.7
通讯作者：
Licht, Christoph
中科院分区：
文献类型：
--
作者：
Riedl, Magdalena;Fakhouri, Fadi;Licht, Christoph
血栓性微血管病（TMA）是一种罕见但严重的疾病，其特征是内皮细胞活化和血栓形成。表现为溶血性贫血、血小板减少和器官衰竭三联征。及时诊断和治疗对长期结果至关重要。TMA通常在感染事件后出现，其中（肠出血性）大肠杆菌是最常见的报告。TMA也发生在补体系统的遗传/自身免疫缺陷（非典型溶血性尿毒综合征[阿胡斯]）和基础疾病（如妊娠、移植、药物、其他肾小球病、血管炎或代谢缺陷）的背景下。补体激活或其调节缺陷现已在越来越多的获得性TMA疾病中描述。与补体介导的疾病谱的扩大相一致，出现了哪些患者可能从补体靶向治疗中受益的问题。治疗的成功取决于补体激活在疾病发病机制中的个体贡献。依库珠单抗（一种阻断末端补体激活的单克隆抗体）的出现显著改善了阿胡斯患者的结局和生活质量。这篇综述讨论了补体的贡献，并强调了其与炎症，凝血和内皮细胞的复杂相互作用。治疗经验侧重于依库珠单抗治疗详细讨论了整个新兴的补体介导的血栓性微血管病谱。
Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by endothelial cell activation and thrombus formation. It manifests with the triad of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and treatment initiation are crucial for long-term outcome. TMA often manifests subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is the most frequently reported. TMA also occurs on the background of genetic/autoimmune defects in the complement system (atypical hemolytic uremic syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation, drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement activation or defects in its regulation have now been described in an increasing number of acquired diseases with TMA. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises which patients might benefit from a complement-targeted therapy. Success of therapy depends on the individual contribution of complement activation in disease pathogenesis. The advent of eculizumab, a monoclonal antibody that blocks terminal complement activation, has markedly improved outcome and quality of life in patients with aHUS. This review discusses the contribution of complement and highlights its complex interaction with inflammation, coagulation, and the endothelium. Treatment experiences focusing on eculizumab therapy are discussed in detail across the emerging spectrum of complement-mediated thrombotic microangiopathies.