Perinatology Research Branch, Division of Obstetric and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
J Matern Fetal Neonatal Med. 2022 Jan;35(2):316-329. doi: 10.1080/14767058.2020.1716720. Epub 2020 Feb 2.
The Fas/Fas ligand (FASL) system and Elabela-apelin receptor signaling pathways are implicated in the pathophysiology of preeclampsia. The aim of the current study was to investigate whether a model combining the measurement of sFas and Elabela in the maternal circulation may serve as a clinical biomarker for early- and/or late-onset preeclampsia more effectively than measures of each biomarker individually.
Blood samples were collected from 214 women in the following groups: (1) normal pregnancy sampled <34 weeks of gestation ( = 56); (2) patients who developed early-onset preeclampsia ( = 54); (3) normal pregnancy sampled ≥34 weeks of gestation ( = 52); (4) patients who developed late-onset preeclampsia ( = 52). Maternal circulating soluble Fas and Elabela concentrations were determined using sensitive and validated immunoassays. Two sample -tests, multivariate logistic regression, and receiver operating characteristic curves were used for analyses.
(1) Women with early-onset preeclampsia, and those with late-onset preeclampsia with placental lesions of maternal vascular malperfusion, had increased concentrations of sFas compared to their gestational age-matched normal controls; (2) women with late-onset preeclampsia, but not those with early-onset preeclampsia, had increased concentrations of Elabela compared to their gestational age-matched counterparts; and (3) an increase in both Elabela and sFas concentrations was more strongly associated with late-onset preeclampsia than early-onset preeclampsia relative to models including either of the markers alone.
A combined model of maternal sFas and Elabela concentrations provides a stronger association with late-onset preeclampsia than either protein alone. This finding demonstrates the possibility to improve the classification of late-onset preeclampsia by combining the results of both molecular biomarkers.
Fas/Fas 配体（FASL）系统和 Elabela-apelin 受体信号通路与子痫前期的病理生理学有关。本研究旨在探讨联合检测母体循环中可溶性 Fas（sFas）和 Elabela 是否比单独检测每种生物标志物更能有效地作为早发型和/或晚发型子痫前期的临床生物标志物。
采集 214 名妇女的血样，分为以下几组：（1）<34 孕周正常妊娠（ = 56）；（2）早发型子痫前期患者（ = 54）；（3）≥34 孕周正常妊娠（ = 52）；（4）晚发型子痫前期患者（ = 52）。采用敏感和验证的免疫测定法测定母体循环中可溶性 Fas 和 Elabela 的浓度。采用两样本检验、多变量逻辑回归和受试者工作特征曲线进行分析。
（1）与胎龄匹配的正常对照组相比，早发型子痫前期患者和伴有母体血管功能不全性胎盘病变的晚发型子痫前期患者的 sFas 浓度升高；（2）与胎龄匹配的对照组相比，晚发型子痫前期患者的 Elabela 浓度升高，但早发型子痫前期患者无此变化；（3）与仅包括其中一种标志物的模型相比，Elabela 和 sFas 浓度的同时升高与晚发型子痫前期的相关性更强，而不是早发型子痫前期。
母体 sFas 和 Elabela 浓度的联合模型与晚发型子痫前期的相关性强于单独使用任何一种蛋白。这一发现表明，通过联合两种分子生物标志物的结果，有可能改善晚发型子痫前期的分类。
