Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn
Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn
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DOI：
10.1016/j.imbio.2014.11.003
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发表时间：
2015-04-01
期刊：
影响因子：
2.8
通讯作者：
Mollnes, Tom Eirik
中科院分区：
文献类型：
--
作者：
Hallstensen, Randi Fykse;Bergseth, Grethe;Mollnes, Tom Eirik
Eculizumab是一种人源IgG2/4嵌合抗补体C5抗体，用于治疗阵发性夜间血红蛋白尿（PNH）或非典型溶血性尿毒症综合征患者。本研究的目的是评估接受eculizumab治疗的孕妇所生新生儿的补体活性是否受损。研究人员开发了一种新的eculizumab-C5复合物（E-C5）特异性检测方法，结果显示，在接受eculizumab治疗的PNH母亲中，两名新生儿携带的E-C5仅为6-7%。孕妇血清完全缺乏终末补体途径活性，而新生儿血清补体活性完全正常。将孕妇及其新生儿的数据与年龄匹配的健康女性对照组和健康新生儿的数据以及未接受治疗的PNH孕妇及其新生儿的数据进行比较。这些都显示正常的补体活性，没有检测到E-C5复合物。此外，新生儿中缺乏eculizumab或E-C5不能解释为缺乏eculizumab与新生儿Fc受体（FcRn）结合，因为eculizumab在体外与受体强烈结合。总之，尽管与FcRn结合，eculizumab和E-C5都不会在胎儿血浆中积累，而且妊娠期eculizumab治疗不会损害新生儿的补体功能。(C) 2014年作者。Elsevier GmbH出版。
Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn. (C) 2014 The Authors. Published by Elsevier GmbH.