单管多重标志物测定法用于估计子痫前期的发病风险。

Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia.

机构信息

Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.

SYNLAB Eesti OÜ, Tallinn 11313, Estonia.

出版信息

J Appl Lab Med. 2020 Nov 1;5(6):1156-1171. doi: 10.1093/jalm/jfaa054.

DOI:10.1093/jalm/jfaa054

PMID:32395752

Abstract

BACKGROUND

Preeclampsia (PE) affects 2%-8% of all pregnancies worldwide. The predictive value of the currently used maternal serum fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) test is < 40% for PE onset within 4 weeks. We aimed to develop an innovative multiplex assay to improve PE prediction.

METHODS

The 6PLEX assay combining the measurements of ADAM12, sENG, leptin, PlGF, sFlt-1, and PTX3 was developed for the Luminex® xMAP platform. Assay performance was evaluated using 61 serum samples drawn from 53 pregnant women between 180 and 275 gestational days: diagnosed PE cases, n = 4; cases with PE onset within 4-62 days after sampling, n = 25; controls, n = 32. The B·R·A·H·M·S Kryptor sFlt-1/PlGF test (Thermo Fisher Scientific, Hennigsdorf, Germany) was applied as an external reference. Alternative PE prediction formulae combining 6PLEX measurements with clinical parameters were developed.

RESULTS

There was a high correlation in sFlt-1/PlGF estimated for individual sera between the 6PLEX and B·R·A·H·M·S Kryptor immunoassays (Spearman's r = 0.93, P < 0.0001). The predictive power of the 6PLEX combined with gestational age and maternal weight at sampling reached AUC 0.99 (95% CI 0.97-1.00) with sensitivity 100.0% and specificity 96.9%. In all models, sFlt-1/PlGF derived from the B·R·A·H·M·S immunoassays exhibited the lowest AUC value (<0.87) and sensitivity (<80%) with broad confidence intervals (13%-92%). The estimated prognostic yield of the 6PLEX compared to the B·R·A·H·M·S assay was significantly higher (96.5% vs 73.7%; P = 0.0005).

CONCLUSIONS

The developed single-tube multimarker assay for PE risk estimation in combination with clinical symptoms reached high prognostic yield (96.5%) and exhibited superior performance compared to the sFlt-1/PlGF test.

摘要

背景

子痫前期（PE）影响全球 2%-8%的妊娠。目前使用的母体血清 fms 样酪氨酸激酶-1/胎盘生长因子（sFlt-1/PlGF）检测对 4 周内发生的 PE 的预测价值<40%。我们旨在开发一种创新的多重分析方法来改善 PE 预测。

方法

在 Luminex®xMAP 平台上开发了一种结合 ADAM12、sENG、瘦素、PlGF、sFlt-1 和 PTX3 测量的 6PLEX 分析。使用来自 180 至 275 天妊娠的 53 名孕妇的 61 份血清样本评估分析性能：诊断为 PE 的病例，n=4；PE 病例在采样后 4-62 天内发病，n=25；对照组，n=32。应用 B·R·A·H·M·S Kryptor sFlt-1/PlGF 检测（Thermo Fisher Scientific，Hennigsdorf，德国）作为外部参考。还开发了结合 6PLEX 测量值和临床参数的替代 PE 预测公式。

结果

个体血清中 sFlt-1/PlGF 的估计值在 6PLEX 和 B·R·A·H·M·S Kryptor 免疫测定之间存在高度相关性（Spearman's r=0.93，P<0.0001）。6PLEX 与孕龄和采样时的母体体重相结合的预测能力达到 AUC 0.99（95%CI 0.97-1.00），灵敏度 100.0%，特异性 96.9%。在所有模型中，来自 B·R·A·H·M·S 免疫测定的 sFlt-1/PlGF 表现出最低的 AUC 值（<0.87）和灵敏度（<80%），置信区间较宽（13%-92%）。与 B·R·A·H·M·S 检测相比，6PLEX 的估计预后获益明显更高（96.5%比 73.7%；P=0.0005）。