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TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy.

ABSTRACT: The present study evaluated maternal plasma protein profiles before the onset of hypertensive disorders of pregnancy (HDP) to assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and HDP before 20 weeks gestation and to evaluate the discriminatory performance of plasma TRAIL levels for HDP.A 2-phase discovery/validation study was designed. In the discovery phase, a nested case-controlled study was performed using plasma sampled at 8 to 20 weeks gestation from 20 women who later developed HDP and from 20 age- and gestational week-matched controls. Plasma was analyzed using a human protein microarray technology designed to simultaneously detect 507 proteins. The functional annotation and clustering of the differentially expressed proteins were performed using DAVID and the GO database. TRAIL levels were further validated in an independent study using plasma obtained at 8 to 20 weeks gestation from 53 women who later developed HDP and from 106 matched controls, and 62 clinical risk factors were investigated.In the protein microarray analysis, 23 proteins were differentially expressed between the two groups. The ELISA showed that women who later developed HDP had significantly lower TRAIL levels compared to women with uncomplicated pregnancies. The multivariable Cox regression analysis identified the following three factors that were entered into the final Cox regression model: gravidity (OR = 2.02, 95% CI 1.00-4.09), pre-pregnancy BMI (OR = 1.46, 95% CI 1.21-1.76) and TRAIL levels (OR = 0.97, 95% CI 0.94-0.99). The model had a significantly better discriminatory power (AUC = 0.83, 95% CI 0.75-0.88) compared to TRAIL alone as an independent predictor of HDP (AUC = 0.59, 95% CI 0.51-0.67).Twenty-three differentially expressed proteins before 20 weeks gestation might be associated with the pathogenesis of HDP. Plasma TRAIL levels were associated with the development of HDP, and the combination of plasma TRAIL levels with pre-pregnancy BMI and gravidity had a good discriminatory performance for HDP before 20 weeks gestation.

SUBMITTER: Zhou C

PROVIDER: S-EPMC4451764 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy.

Zhou Cheng C Long Yan Y Yang Hongling H Zhu Chunyan C Ma Qingling Q Zhang Yonggang Y

PloS one 20150601 6

<h4>Objective</h4>The present study evaluated maternal plasma protein profiles before the onset of hypertensive disorders of pregnancy (HDP) to assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and HDP before 20 weeks gestation and to evaluate the discriminatory performance of plasma TRAIL levels for HDP.<h4>Methods</h4>A 2-phase discovery/validation study was designed. In the discovery phase, a nested case-controlled study was perfor ...[more]

PMID: 26030414

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Project description:ObjectThis study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein ?-chain (MSP-?) before the 20th week of gestation for the early diagnosis of preeclampsia (PE).Methods and materialsTwo parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-? plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group).ResultsThe plasma level of MSP-? was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-? level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-? before the 20th week of gestation was 0.905 (95% CI, 0.811-0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 ± 5325.56 vs. 4104.83 ± 2383.06, P = 0.021).ConclusionAccording to the findings of this study, the plasma level of MSP-? may be associated with PE, and MSP-? may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP-? in combination with other protein factors for the early diagnosis of PE.

Dataset Information

TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy.

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TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy.

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