Ten Years of Clinical Experience With Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria
Ten Years of Clinical Experience With Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria
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DOI：
10.1053/j.seminhematol.2018.04.001
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发表时间：
2018-07-01
影响因子：
3.6
通讯作者：
de latour, Regis Peffault
中科院分区：
文献类型：
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作者：
de Fontbrune, Flore Sicre;de latour, Regis Peffault
阵发性夜间血红蛋白尿（PNH）由磷脂酰肌醇聚糖a类x连锁基因的体细胞突变引起，该基因导致糖基磷脂酰肌醇锚定蛋白的缺乏。糖基磷脂酰肌醇锚定蛋白补体调节蛋白（CD59）之一的缺失导致溶血。临床表现包括慢性溶血、血栓栓塞性疾病、感染性并发症、慢性肾损伤、肺动脉高压、平滑肌功能障碍等。直到10年前，治疗主要是支持性的，与年龄匹配的对照组相比，大多数患者的发病率很高，生存期缩短。eculizumab是一种针对终末补体蛋白C5的人源化单克隆抗体，其开发显著提高了患者的生存率并减少了并发症。在这篇文章中，我们回顾了10年来eculizumab治疗PNH的临床经验以及具体的相关情况。血管外溶血和eculizumab在妊娠PNH患者中的应用也得到了解决。(C) 2018爱思唯尔公司版权所有。
Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation in the phosphatidylinositol glycan class A, X-linked gene, responsible for a deficiency in glycosyl phosphatidylinositol-anchored proteins. The absence of one of the glycosyl phosphatidylinositol-anchored protein complement regulatory proteins (CD59) leads to hemolysis. Clinical manifestations include chronic hemolysis, thromboembolic disease, infectious complications, chronic kidney injury, pulmonary hypertension, and smooth muscle dysfunction. Until 10 years ago, treatment was mainly supportive, with most patients suffering from significant morbidity and shortened survival compared with age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has led to dramatic improvements in survival and reduced complications. In this article, we review 10 years of clinical experience with eculizumab in PNH along with specific related situations. Extravascular hemolysis and the use of eculizumab in pregnant patients with PNH are also addressed. (C) 2018 Elsevier Inc. All rights reserved.