Stefanovic Vedran
Department of Obstetrics and Gynecology, Helsinki University and Helsinki University Hospital, Haartmaninkatu 2, 00290 Helsinki, Finland.
J Clin Med. 2019 Mar 24;8(3):407. doi: 10.3390/jcm8030407.
Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring.
补体过度激活参与多种疾病的发病机制，而肾脏是对补体介导的损伤特别敏感的器官。除阵发性夜间血红蛋白尿（PNH）和非典型溶血尿毒综合征（aHUS）外，还有其他几种疾病有明确证据表明补体激活在孕期影响母体和胎儿的肾脏，并导致长期不良后果。最近已开发出几种用于阻断补体级联反应的新型药物，包括纯化的血浆蛋白、新型单克隆抗体、重组蛋白、小分子和小分子干扰RNA制剂。依库珠单抗是一种靶向C5的人源化单克隆IgG2/4抗体，于2007年被美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准用于治疗两种罕见疾病：PNH和2011年的aHUS。越来越多关于依库珠单抗用于非标签适应症（如患有抗磷脂综合征、镰状细胞贫血和HELLP综合征的孕妇）获得成功的报道。这些严重疾病与高孕产妇和胎儿发病率、死亡率以及大量早产相关。依库珠单抗已显著改善PNH和aHUS患者的总体预后，使许多女性能够安全怀孕。延长孕期并使用依库珠单抗，即使仅使用几周，不仅可以保护母体肾功能，还可以减轻后代早产的急性和长期肾脏后果。
