Nuffield Department of Women's and Reproductive Health, University of Oxford, United Kingdom (S.J., W.Z., M.R., W.C., C.R., M.V.).
The Key Laboratory of Molecular Medicine of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Jiangxi, China (Q.C.).
Hypertension. 2023 Jul;80(7):1439-1451. doi: 10.1161/HYPERTENSIONAHA.123.20907. Epub 2023 May 25.
Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Identifying women with high risk of developing preeclampsia in early pregnancy remains challenging. Extracellular vesicles released from the placenta offer an attractive biomarker but have been elusive to quantify.
Here, we tested ExoCounter, a novel device that immunophenotypes size-selected small extracellular vesicles <160 nm, for its ability to perform qualitative and quantitative placental small extracellular vesicles (psEV) analysis. To investigate disease-specific and gestational age-specific changes, we analyzed psEV counts in maternal plasma samples taken at each of the 3 trimesters from women who had (1) normal pregnancy (n=3); (2) women who developed early-onset preeclampsia (EOPE; n=3); and (3) women who developed late-onset preeclampsia (n=4) using 3 antibody pairs, CD10-placental alkaline phosphatase (PLAP), CD10-CD63, and CD63-PLAP. We further validated the findings in first-trimester serum samples among normal pregnancy (n=9), women who developed EOPE (n=7), and women who developed late-onset preeclampsia (n=8).
We confirmed that CD63 was the major tetraspanin molecule coexpressed with PLAP-a known placental extracellular vesicles marker on psEV. Higher psEV counts for all 3 antibody pairs were detected in the plasma of women who developed EOPE than the other 2 groups in the first trimester, which persisted through the second and third trimesters. Significantly higher CD10-PLAP (<0.01) and CD63-PLAP (<0.01) psEV counts were validated in the serum of the first trimester of women who developed EOPE compared with normal pregnancy.
Application of the ExoCounter assay developed here could identify patients at risk of developing EOPE in the first trimester, thereby providing a window of opportunity for early intervention.
子痫前期是全球孕产妇和围产儿发病率和死亡率的主要原因。在早期妊娠时识别出有发生子痫前期高风险的妇女仍然具有挑战性。胎盘释放的细胞外囊泡提供了有吸引力的生物标志物，但一直难以定量。
在这里，我们测试了 ExoCounter，一种新型设备，用于对大小选择的小细胞外囊泡<160nm 进行免疫表型分析，以评估其进行定性和定量胎盘小细胞外囊泡（psEV）分析的能力。为了研究疾病特异性和妊娠龄特异性变化，我们分析了来自于 3 组女性的母体血浆样本中的 psEV 计数，这 3 组女性分别为：(1) 正常妊娠（n=3）；(2) 发生早发型子痫前期（EOPE；n=3）；和 (3) 发生晚发型子痫前期（n=4）。我们使用 3 种抗体对（CD10-胎盘碱性磷酸酶 (PLAP)、CD10-CD63 和 CD63-PLAP）对每个妊娠期中的样本进行了分析。我们还在正常妊娠（n=9）、发生 EOPE（n=7）和发生晚发型子痫前期（n=8）的女性的第一孕期血清样本中进一步验证了这些发现。
我们证实 CD63 是与 PLAP 共表达的主要四跨膜蛋白分子 - 已知的胎盘细胞外囊泡标志物，在第一孕期中，发生 EOPE 的女性的所有 3 种抗体对的 psEV 计数均高于其他 2 组，这种情况一直持续到第二和第三孕期。在发生 EOPE 的女性的第一孕期血清中，CD10-PLAP（<0.01）和 CD63-PLAP（<0.01）的 psEV 计数显著更高，与正常妊娠相比差异具有统计学意义。
应用这里开发的 ExoCounter 测定法可以在第一孕期识别出有发生 EOPE 风险的患者，从而为早期干预提供机会。
