Maternal plasma concentrations of the soluble tumor necrosis factor receptor 2 are increased prior to the diagnosis of preeclampsia.
Maternal plasma concentrations of the soluble tumor necrosis factor receptor 2 are increased prior to the diagnosis of preeclampsia.
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DOI：
10.1016/j.ajog.2009.01.033
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发表时间：
2009-06
影响因子：
9.8
通讯作者：
Meis, Paul
中科院分区：
文献类型：
--
作者：
Sibai, Baha;Romero, Roberto;Klebanoff, Mark A.;Rice, Madeline Murguia;Caritis, Steve;Lindheimer, Marshall D.;Van Dorsten, J. Peter;Landon, Mark;Miodovnik, Menachem;Dombrowski, Mitchell;Meis, Paul
循环肿瘤坏死因子-α是一种能激活内皮细胞及其可溶性受体的促炎细胞因子，在明显的子痫前期中升高，这与增强全身炎症反应和内皮细胞功能障碍在子痫前期综合征的病理生理过程中的重要假设是一致的。如果是这样的话，这种水平的上升应该在疾病发生之前。本研究旨在研究在子痫前期发病前，血浆中sTNF-R1和sTNF-R2的浓度是否升高。这是一项对NICHD子痫前期预防试验中储存的母体血浆进行的回溯性生物标记物研究，该试验在有先兆子痫危险因素的患者中进行，以测试小剂量阿司匹林与安慰剂的疗效。第一次采集于妊娠13~26周，第二次采集于妊娠24~28周。用灵敏和特异的免疫分析方法对1004例患者进行了系列sTNF-R1和sTNF-R2浓度的评估，这两个样本都是采集的。子痫前期发生率为21.3%(214/1004)。先兆子痫患者在13-26周(样本1)和24-28周(样本2)的血浆sTNF-R2中位数水平显著高于未患子痫前期的患者(样本1：sTNF-R2中位数2,678 pg/ml，范围934-7,835对中位数2,535 pg/ml，范围1,022-13,000，p=0.02；sTNF-R1：中位数936 pg/ml，范围449-3,239对中位数913 pg/ml，范围359-5,060，p=0.19)。从样本1到样本2，sTNF-R2增加的先兆子痫的几率显著增加(OR=每1000个单位增加1.23)。与sTNF-R2基因第四个四分位数的女性相比，24-28周的女性患先兆子痫的调整后优势显著增加(OR=1.55，95%CI=1.02-2.35，p=0.04)。然而，这种联系因治疗组(阿司匹林或安慰剂)而异。没有观察到sTNF-R1的相关性。STNF-R2和sTNF-R1的敏感性和阳性预测值均较低。母血sTNF-R2浓度升高先于子痫前期的临床表现。这些观察表明，促炎细胞因子水平在显性疾病发生之前很久就会升高，并可能在先兆子痫的发病机制中起作用。
Circulating tumor necrosis factor-alpha (TNF-α), a potent pro-inflammatory cytokine, capable of activating endothelial cells, as well as its soluble receptors (sTNF-R1 and sTNF-R2), is increased during overt preeclampsia, consistent with hypotheses that enhanced systemic inflammatory response and endothelial cell dysfunction are important in the pathophysiology of the preeclamptic syndrome. If so, such increases in levels should precede the onset of the disease. This study was designed to examine whether plasma concentrations of sTNF-R1 and sTNF-R2 are elevated prior to the onset of preeclampsia. This was a retrospective biomarker study of stored maternal plasma from an NICHD preeclampsia prevention trial conducted in patients with risk factors for developing preeclampsia to test the effectiveness of low dose aspirin compared with placebo. The first sample was collected at 13–26 weeks’ gestation and the second at 24–28 weeks’ gestation. Serial sTNF-R1 and sTNF-R2 concentrations were assessed using sensitive and specific immunoassays in 1,004 patients in whom both samples were collected. The incidence of preeclampsia was 21.3% (214/1004). Median plasma levels of the sTNF-R2, but not sTNF-R1, were significantly higher at 13–26 weeks (sample 1) and at 24–28 weeks (sample 2) in patients who developed preeclampsia than in those who did not (sample 1: sTNF-R2: median 2,678 pg/ml, range 934–7,835 vs. median 2,535 pg/ml, range 1,022–13,000, p=0.02; sTNF-R1: median 936 pg/ml, range 449–3,239 vs. median 913 pg/ml, range 359–5,060, p=0.19). There was a significantly increased odds of preeclampsia for an increase in sTNF-R2 from sample 1 to sample 2 (OR=1.23 per 1,000 unit increase). Women in the fourth quartile of sTNF-R2 at 24–28 weeks, had a significantly increased adjusted odds of preeclampsia (OR=1.55, 95%CI=1.02–2.35, p=0.04), compared with women in the first quartile. This association, however, varied by treatment group (aspirin or placebo). No association was observed for sTNF-R1. The sensitivity and positive predictive values were low for sTNF-R2, as well as sTNF-R1. An increase in maternal plasma sTNF-R2 concentration precedes clinical manifestation of preeclampsia. These observations demonstrate that levels of proinflammatory cytokines rise well before development of overt disease and could be operative in the pathogenic mechanisms responsible for preeclampsia.
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影响因子：
7.2
作者：
Kupferminc, MJ;Peaceman, AM;Socol, ML
通讯作者：
Socol, ML
影响因子：
158.5
作者：
Caritis, S;Sibai, B;Thurnau, G
通讯作者：
Thurnau, G
DOI：
10.1046/j.1525-1373.1999.d01-139.x
发表时间：
1999-12-01
影响因子：
--
作者：
Hubel, CA
通讯作者：
Hubel, CA
影响因子：
15.9
作者：
Aderka, D;Sorkine, P;Klausner, J
通讯作者：
Klausner, J
DOI：
10.1073/pnas.89.11.4845
发表时间：
1992-06-01
影响因子：
11.1
作者：
VANZEE, KJ;KOHNO, T;LOWRY, SF
通讯作者：
LOWRY, SF