Antibody Treatment Promotes Compensation for Human Cytomegalovirus-Induced Pathogenesis and a Hypoxia-Like Condition in Placentas with Congenital Infection
Antibody Treatment Promotes Compensation for Human Cytomegalovirus-Induced Pathogenesis and a Hypoxia-Like Condition in Placentas with Congenital Infection
复制标题
DOI：
10.2353/ajpath.2010.091210
复制
发表时间：
2010-09-01
影响因子：
6
通讯作者：
Pereira, Lenore
中科院分区：
文献类型：
--
作者：
Maidji, Ekaterina;Nigro, Giovanni;Pereira, Lenore
人巨细胞病毒（HCMV）是世界范围内出生缺陷的主要病毒原因。受影响的婴儿可能会有暂时的症状，出生后不久就解决了，如生长受限，和永久性残疾，包括神经损伤。对原发性HCMV感染的孕妇进行被动免疫是预防先天性疾病的一种有希望的治疗方法。为了了解持续病毒复制对胎盘的影响和保护性抗体的被动转移，我们对来自未经治疗的先天性感染、HCMV特异性超免疫球蛋白治疗和未感染对照的妇女的胎盘标本进行了免疫组织学分析。在未经治疗的感染，病毒复制蛋白被发现在滋养层和绒毛和子宫动脉的内皮细胞。相关的损害包括广泛的纤维素样沉积、纤维化、无血管绒毛和水肿，这可能损害胎盘功能。血管内皮生长因子及其受体鳍状酪氨酸激酶1（Flt 1）上调，羊水中含有较高水平的可溶性FM（sFlt 1），一种1298抗血管生成蛋白，相对于胎盘生长因子。用高免疫球蛋白治疗，胎盘出现未感染，血管内皮生长因子和Flt 1表达减少，羊水中sFlt 1水平较低。绒毛膜绒毛和血管的数量增加，在控制建议代偿性发展的缺氧样条件。总之，结果表明，抗体治疗可以抑制HCMV复制和预防胎盘功能障碍，从而改善胎儿结局。(Am J Pathol 2010. 177：1298-1310。（见10.2353/ajpatb.2010.091210）
Human cytomegalovirus (HCMV) is the major viral cause of birth defects worldwide. Affected infants can have temporary symptoms that resolve soon after birth, such as growth restriction, and permanent disabilities, including neurological impairment. Passive immunization of pregnant women with primary HCMV infection is a promising treatment to prevent congenital disease. To understand the effects of sustained viral replication on the placenta and passive transfer of protective antibodies, we performed immunohistological analysis of placental specimens from women with untreated congenital infection, HCMV-specific hyperimmune globulin treatment, and uninfected controls. In untreated infection, viral replication proteins were found in trophoblasts and endothelial cells of chorionic villi and uterine arteries. Associated damage included extensive fibrinoid deposits, fibrosis, avascular villi, and edema, which could impair placental functions. Vascular endothelial growth factor and its receptor fins-like tyrosine kinase 1 (Flt1) were up-regulated, and amniotic fluid contained elevated levels of soluble FM (sFlt1), an 1298 antiangiogenic protein, relative to placental growth factor. With hyperimmune globulin treatment, placentas appeared uninfected, vascular endothelial growth factor and Flt1 expression was reduced, and sFlt1 levels in amniotic fluid were lower. An increase in the number of chorionic villi and blood vessels over that in controls suggested compensatory development for a hypoxia-like condition. Taken together the results indicate that antibody treatment can suppress HCMV replication and prevent placental dysfunction, thus improving fetal outcome. (Am J Pathol 2010. 177:1298-1310. 10.2353/ajpatb.2010.091210)