Dataset Information

Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes.

ABSTRACT: The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n?=?101), preeclampsia (PE, n?=?55) and gestational diabetes (GDM, n?=?36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193-7938 vs. 1093, IQR 395-5689; p?=?0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67-0.93; p?=?0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.

SUBMITTER: Kussel L

PROVIDER: S-EPMC5648869 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes.

Küssel Lorenz L Herkner Harald H Wahrmann Markus M Eskandary Farsad F Doberer Konstantin K Binder Julia J Pateisky Petra P Zeisler Harald H Böhmig Georg A GA Bond Gregor G

Scientific reports 20171019 1

The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increa ...[more]

PMID: 29051520

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Project description:IntroductionPreeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures.Material and methodsWe measured 91 metabolites by high-throughput nuclear magnetic resonance spectroscopy at four time points (visits) during pregnancy (weeks 14-16, 22-24, 30-32 and 36-38). Samples were taken from a Norwegian pregnancy cohort. We fitted a linear regression model for each metabolic measure to compare women who developed preeclampsia (n = 38) and healthy controls (n = 70).ResultsAmong women who developed preeclampsia, 92% gave birth after 34 weeks of gestation. Compared to women with healthy pregnancies, women who developed preeclampsia had higher levels of several lipid-related metabolites at visit 1, whereas fewer differences were observed at visit 2. At visit 3, the pattern from visit 1 reappeared. At visit 4 the differences were larger in most subgroups of very-low-density lipoprotein particles, the smallest high-density lipoprotein, total lipids and triglycerides. Total fatty acids were also increased, of which monounsaturated fatty acids and saturated fatty acids showed more pronounced differences. Concentration of glycine tended to be lower in pregnancies with preeclampsia until visit 3, although this was not significant after correction for multiple testing. After adjustment for age, BMI, parity and gestational weight gain, all significant differences were attenuated at visits 1 and 2. The estimates were less affected by adjustment at visits 3 and 4.ConclusionsIn early pregnancy, the metabolic differences between preeclamptic and healthy pregnancies were primarily driven by maternal BMI, probably representing the women's pre-pregnancy metabolic status. In early third trimester, several weeks before clinical manifestation, the differences were less influenced by BMI, indicating preeclampsia-specific changes. Near term, women with preeclampsia developed an atherogenic metabolic profile, including elevated total lipids, very-low-density lipoprotein, triglycerides, and total fatty acids.

Project description:Preeclampsia is one of the most severe gestational complications which is one of the leading causes of maternal and perinatal morbidity and mortality. A growth in the incidence of severe and combined forms of the pathology has been observed in recent years. According to modern concepts, inadequate cytotrophoblast invasion into the spiral arteries of the uterus and development of the ischemia-reperfusion syndrome in the placental tissue play the leading role in the development of preeclampsia, which is characterized by multipleorgan failure. In this regard, our work was aimed at studying the patterns of placental tissue transcriptome that are specific to females with PE and with physiological pregnancy, as well as identifying the potential promising biomarkers and molecular mechanisms of this pathology. We have identified 63 genes whose expression proved to differ significantly in the placental tissue of females with PE and with physiological pregnancy. A cluster of differentially expressed genes (DEG) whose expression level is increased in patients with preeclampsia includes not only the known candidate genes that have been identified in many other genome-wide studies (e.g., LEP, BHLHB2, SIGLEC6, RDH13, BCL6), but also new genes (ANKRD37, SYDE1, CYBA, ITGB2, etc.), which can be considered as new biological markers of preeclampsia and are of further interest. The results of a functional annotation of DEG show that the development of preeclampsia may be related to a stress response, immune processes, the regulation of cell-cell interactions, intracellular signaling cascades, etc. In addition, the features of the differential gene expression depending on preeclampsia severity were revealed. We have found evidence of the important role of the molecular mechanisms responsible for the failure of immunological tolerance and initiation of the pro-inflammatory cascade in the development of severe preeclampsia. The results obtained elaborate the concept of the pathophysiology of preeclampsia and contain the information necessary to work out measures for targeted therapy of this disease. ;

Project description:BACKGROUND:Gestational diabetes mellitus (GDM) is correlated with an increased risk of adverse perinatal outcomes for both the mother and offspring. Previous research has reported correlations between maternal dietary patterns and GDM, but such evidence for twin pregnancies is lacking. This study aimed to identify maternal dietary patterns in the second trimester and investigate their relationships with the risk of GDM among women who were pregnant with twins in China. METHODS:A longitudinal twin pregnancies birth cohort study of women who were pregnant with twins in China was conducted. Maternal dietary intake in the second trimester was recorded by using a food frequency questionnaire prior to the diagnosis of GDM among participants from the prospective twin pregnancies birth cohort in Chongqing City. GDM was diagnosed with a 75?g 2-h oral glucose tolerance test at 23-26?weeks of gestation. Dietary patterns were identified by principal components analysis, and the correlations between dietary pattern and GDM were examined using multivariable logistic regression analyses. RESULTS:Of the 324 participants, 101 (31.2%) were diagnosed with GDM. Four dietary patterns were identified: a vegetable-based pattern, a poultry-and-fruit-based pattern, a sweet-based pattern and a plant-protein-based pattern. Multivariate analysis showed that none of the dietary patterns were correlated with the risk of GDM among women who were pregnant with twins, but the sweet-based dietary pattern, which was associated with a higher GDM risk for quartile 4 versus quartile 1 (OR 2.69; 95% CI: 1.09, 6.66) among non-overweight women (prepregnancy BMI?<?24.0). CONCLUSION:Dietary patterns were not correlated with later GDM risk among women who were pregnant with twins in western China, whereas a high intake of sweets was associated with a higher risk for GDM among women who were not overweight prior to pregnancy. TRIAL REGISTRATION:ChiCTR-OOC-16008203. Retrospectively registered on 1 April 2016.

Dataset Information

Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes.

Publications

Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes.

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