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鉴定早期预测子痫前期的新型孕早期血清生物标志物。

Identification of novel first-trimester serum biomarkers for early prediction of preeclampsia.

发表日期:2023 Sep 18
作者: Mingxi Liu, Yue Niu, Kongyang Ma, Peter C K Leung, Zi-Jiang Chen, Daimin Wei, Yan Li
来源: Journal of Translational Medicine

摘要:

子痫前期(PE)是全球母婴死亡和发病率的主要原因之一,但由于缺乏可靠的生物标志物,有效的早期预测仍然具有挑战性。基于我们大规模辅助生殖队列平台的广泛人类生物库,测量了34位被诊断为PE的女性和34位匹配的正常血压对照组的第一孕期血清中48种细胞因子、总免疫球蛋白(Ig)、抗磷脂酰丝氨酸(aPS)抗体以及一些先前报道的PE生物标志物(包括胎盘生长因子(PlGF)、可溶性fms样酪氨酸激酶-1(sFlt-1)和活化素A)的水平。与对照组相比,PE组的第一孕期血清中白细胞介素(IL)-2Rα、IL-9、肿瘤坏死因子-β(TNF-β)、RANTES、肝细胞生长因子(HGF)、总IgM和总IgG以及aPS IgG光密度(OD)值显著增高,而第一孕期血清中PlGF、总IgA以及aPS-IgG免疫复合物(IC)OD值显著降低。将前五个第一孕期血清生物标志物(总IgM、总IgG、PlGF、aPS IgG和总IgA)组合起来,与独立使用PlGF和PlGF/sFlt-1相比,对PE的发展具有更好的预测价值[曲线下面积(AUC)及95%置信区间(CI)为0.983(0.952-1.000),敏感性为100%,特异性为94.1%]。我们鉴定了新的第一孕期血清生物标志物,并利用免疫相关因子和PlGF开发了一个有效的第一孕期预测模型,用于PE,这有助于早期诊断策略的发展,并为进一步探索PE的机制提供免疫学上的见解。©2023. BioMed Central Ltd., Springer Nature的一部分。
Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers.Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously reported PE biomarkers [including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A] were measured in 34 women diagnosed with PE and 34 matched normotensive controls.The PE group has significantly higher first-trimester serum levels of interleukin (IL)-2Rα, IL-9, tumor necrosis factor-β (TNF-β), RANTES, hepatocyte growth factor (HGF), total IgM, and total IgG, and aPS IgG optical density (OD) value, as well as lower first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value than the control group. Combining top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI) 0.983 (0.952-1.000), with a sensitivity of 100% and a specificity of 94.1%] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively].We identified novel first-trimester serum biomarkers and developed an effective first-trimester prediction model using immune-related factors and PlGF for PE, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.© 2023. BioMed Central Ltd., part of Springer Nature.