Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies.

Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies.
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DOI:
10.1136/lupus-2015-000134
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发表时间:
2016
影响因子:
3.9
通讯作者:
Lieberman RW
Lieberman RW
中科院分区:
医学3区
文献类型:
--
作者:
Marder W;Knight JS;Kaplan MJ;Somers EC;Zhang X;O'Dell AA;Padmanabhan V;Lieberman RW

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系统性红斑狼疮(SLE)与不良妊娠结局(包括先兆子痫)风险增加相关,特别是与抗磷脂抗体综合征(APS)相关。虽然在子痫前期会出现明显的胎盘异常,但对狼疮活动和妊娠期APS如何影响胎盘的了解较少。我们描述了狼疮妊娠人群的胎盘病理,其中一些合并aps相关血栓,其中先兆子痫和其他并发症的发展。我们进行了标准的胎盘组织病理学检查,并定量了绒毛间隙的中性粒细胞和中性粒细胞胞外陷阱(NETs),因为NETs与狼疮、APS和先兆子痫有公认的联系。对子痫前期、SLE和对照胎盘进行组织学特征评分,并对中性粒细胞进行H&E定量,对颗粒蛋白髓过氧化物酶进行免疫组化染色。在去致密核的背景下,通过细胞外髓过氧化物酶染色鉴定NETs。使用非参数分析来评估各组间净中性粒细胞和完整中性粒细胞的差异,并使用Kruskal-Wallis检测组织学结果与中性粒细胞之间的关联。对35例妊娠的胎盘进行评估:10例对照组,11例先兆子痫,4例SLE+先兆子痫和10例SLE,其中1例合并灾难性APS, 1例合并妊娠期间肝和脾静脉血栓形成。在狼疮病例中观察到宫内生长受限和羊水过少,而在对照组中没有。在子痫前期、SLE+子痫前期和所有10例SLE非子痫前期患者中,NETs浸润胎盘间隙的比例明显增加。与对照组相比,所有病例组的NETs与总中性粒细胞的比率显著增加。当存在NETs时,NETs与母体血管炎、蜕膜坏死、母胎界面出血和非闭塞性胎儿血栓性血管病变有关。在这项对狼疮妊娠胎盘组织的初步研究中,结果更为复杂,特别是如果与APS相关。胎盘组织显示明显的炎症和血管变化,基本上与子痫前期妊娠的胎盘组织无法区分。
Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, in which pre-eclampsia and other complications developed. We performed standard histopathological placental review and quantified neutrophils and neutrophil extracellular traps (NETs) in the intervillous space, given the recognised association of NETs with lupus, APS and pre-eclampsia. Pre-eclampsia, SLE and control placentas were scored for histological features, and neutrophils were quantified on H&E and immunohistochemical staining for the granular protein myeloperoxidase. NETs were identified by extracellular myeloperoxidase staining in the setting of decondensed nuclei. Non-parametric analysis was used to evaluate differences in netting and intact neutrophils between groups, with Kruskal–Wallis testing for associations between histological findings and neutrophils. Placentas were evaluated from 35 pregnancies: 10 controls, 11 pre-eclampsia, 4 SLE+pre-eclampsia and 10 SLE, including one complicated by catastrophic APS and one complicated by hepatic and splenic vein thromboses during pregnancy. Intrauterine growth restriction and oligohydramnios were observed in lupus cases but not controls. Significantly more NETs were found infiltrating placental intervillous spaces in pre-eclampsia, SLE+pre-eclampsia and all 10 SLE non-pre-eclampsia cases. The ratio of NETs to total neutrophils was significantly increased in all case groups compared with controls. When present, NETs were associated with maternal vasculitis, laminar decidual necrosis, maternal–fetal interface haemorrhage and non-occlusive fetal thrombotic vasculopathy. In this pilot study of placental tissue from lupus pregnancies, outcomes were more complicated, particularly if associated with APS. Placental tissue revealed marked inflammatory and vascular changes that were essentially indistinguishable from placental tissue of pre-eclampsia pregnancies.