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P42. TNF-ALPHA gene polymorphism in pathology of preeclampsia
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Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 209–258
for C/A genotype and OR = 1.84; 95%CI:0.27–12.35 for A/A homozygote). Although insignificant association between IL-10 592C>A and onset of the PE was assessed, a slight trend for higher prevalence of early form (<34 g.w.) was noted in A allele carriers (OR = 1.37; 95%CI:0.14–13.02). Conclusion: The risk of hypertensive disorders in pregnancy may be elevated among Slovak women with IL-10 592C>A polymorphisms, where the A allele may be associated with severe cases of PE. This work was supported by the project: ‘‘Centre of excellence for perinatology research (CEPV II)’’, ITMS: 26220120036, co-financed by EU sources (100%). doi:10.1016/j.preghy.2015.07.094
P42. TNF-ALPHA gene polymorphism in pathology of preeclampsia Pavol Zubor a, Andrea Mendelova b, Imrich Zigo a, Maria Skerenova c, Eva Jezkova b, Jan Danko a (a Jessenius Medical Faculty, Comenius University, Department of Obstetrics & Gynecology, Martin, Slovakia, b Jessenius Medical Faculty, Comenius University, Institute of Molecular Biology, Martin, Slovakia, c Jessenius Medical Faculty, Comenius University, Department of Medical Biochemistry, Martin, Slovakia) Introduction: Preeclampsia (PE) is a life-threatening complication of pregnancy associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of mother, fetus or both. Objectives: Etiology of PE is still uncertain, however recently the role of immune system takes on importance. Thus the role of central cytokine, tumor necrosis factor (TNF) involved in inflammation processes become widely investigated in obstetric disorders. Following this the present study is to investigate the effect of TNF-alpha gene G308A (rs1800629) polymorphism on disease risk, renal functions, microvascular permeability, endothelial cell dysfunction and organ involvement in women with preeclampsia. Methods: Initially a 102 3rd trimester pregnant women (preeclamptic-cases and healthy controls) with singleton pregnancy were invited for participation of which 76 were genotyped for TNF-alpha G308A polymorphism, evaluated for plasma levels of sVCAM-1, fibronectin, TNF-alpha and correlated to profile of preeclampsia. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to set association between TNF-apolymorphism and PE risk. For continuous variables we applied Student’s t-test and for categorical variables the Pearson x2 or Fisher’s exact test. The two-way ANOVA with Bonferroni correction was used in multivariate analysis. Results: The A allele was more frequent in cases than controls (22.4% vs. 13.2%) what increased disease risk (OR = 2.73). Maternal serum levels of TNF-alpha, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/mL, 1243 ± 671 ng/mL, 0.308 ± 0.231 g/L) compared to controls (301.1 ± 156.1 pg/mL, 651 ± 250 ng/mL, 0.218 ± 0.101 g/L, p < 0.0001, p < 0.0001, p = 0.031; respectively) and levels shoved increasing trend with mutant allele in genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8% vs. 14.3%, p < 0.05 and 13.0% vs. 4.7%, p < 0.01; respectively). The adverse effect of rs1800629 allele A on renal functions was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study revealed possible association between clinical and laboratory manifestations of preeclampsia and TNF-alpha
gene G308A (rs1800629) polymorphism. This work was supported by the project: ‘‘Centre of excellence for perinatology research (CEPV II)’’, ITMS: 26220120036, co-financed by EU sources (100%). doi:10.1016/j.preghy.2015.07.095
P43. Characterization of monocyte phenotype and polarization in preeclampsia and intrauterine fetal growth restriction Thushari Alahakoon a, Heather Medbury b, Helen Williams b, Nicole Fewings b, Xin Wang b, Vincent Lee⁄ c (a Westmead Hospital, Australia, Department of Obstetrics and Gynecology, Sydney, Australia, b University of Sydney, Sydney Medical School, Sydney, Australia, c Westmead Hospital, Australia, Department of Renal Medicine, Sydney, Australia) Introduction: Monocytes can differentiate into various macrophage phenotypes in health and disease, however the phenotype and polarisation of monocytes in pregnancies complicated by preeclampsia and intrauterine growth retardation has not yet been fully characterised. Objectives: To determine if monocyte phenotype and polarization is altered in pregnancy complications such as preeclampsia and fetal growth restriction. Methods: A prospective cross-sectional case control study. Pregnant women between 24 and 40 weeks of gestation were classified into four clinical groups of Normal pregnancy, Preeclampsia, IUGR and preeclampsia with IUGR (PE+IUGR). The maternal venous blood samples were collected pre-delivery/labour using sterile tubes containing an EDTA salt as the anticoagulant. The samples were analyzed within 2 hours of venipuncture. The whole blood sample was processed for flow cytometry. Staining was performed for expression of surface markers – CD14 used for identification of monocytes, CD16 for classification into monocyte subtypes and CD86 and CD163 for classification into phenotypes M1 and M2. The distribution of maternal monocytes subtypes (classical, intermediate and non classical) were characterized and compared for each clinical group. Results: A total of 54 patients were recruited (normal = 24, PE = 9, IUGR = 12, PE+IUGR = 9). The intermediate monocyte percentage was significantly elevated in IUGR compared to normal pregnancy and in both PE and PE+IUGR for gestations <38 weeks. The level of CD163 expression was significantly increased in the PE+IUGR group for all three monocyte subsets compared to both the controls and PE group, as well as increased on the classical and intermediate subsets for the IUGR compared to PE group. Conclusion: We have shown for the first time that there is a shift towards increased intermediate maternal monocyte subtype in IUGR and PE+IUGR as well as polarization of maternal peripheral monocytes (all subsets) towards M2 in pregnancies complicated by IUGR. These changes may represent the body’s response to and repair of significant placental injury. doi:10.1016/j.preghy.2015.07.096
P44. Syncytiotrophoblast extracellular membrane vesicles from preeclamptic placentae show reduced abilities to guide monocyte maturation and activation as well as reduced activation of cytotoxicity of regulatory T-cells and NK-cells Claudia Göhner a, Jolien Fledderus b, Justine Fitzgerald c, Ekkehard Schleußner c, Udo Markert c, Torsten Plösch a, Sicco Scherjon a, Marijke Faas b (a University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, The
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 209–258
for C/A genotype and OR = 1.84; 95%CI:0.27–12.35 for A/A homozygote). Although insignificant association between IL-10 592C>A and onset of the PE was assessed, a slight trend for higher prevalence of early form (<34 g.w.) was noted in A allele carriers (OR = 1.37; 95%CI:0.14–13.02). Conclusion: The risk of hypertensive disorders in pregnancy may be elevated among Slovak women with IL-10 592C>A polymorphisms, where the A allele may be associated with severe cases of PE. This work was supported by the project: ‘‘Centre of excellence for perinatology research (CEPV II)’’, ITMS: 26220120036, co-financed by EU sources (100%). doi:10.1016/j.preghy.2015.07.094
P42. TNF-ALPHA gene polymorphism in pathology of preeclampsia Pavol Zubor a, Andrea Mendelova b, Imrich Zigo a, Maria Skerenova c, Eva Jezkova b, Jan Danko a (a Jessenius Medical Faculty, Comenius University, Department of Obstetrics & Gynecology, Martin, Slovakia, b Jessenius Medical Faculty, Comenius University, Institute of Molecular Biology, Martin, Slovakia, c Jessenius Medical Faculty, Comenius University, Department of Medical Biochemistry, Martin, Slovakia) Introduction: Preeclampsia (PE) is a life-threatening complication of pregnancy associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of mother, fetus or both. Objectives: Etiology of PE is still uncertain, however recently the role of immune system takes on importance. Thus the role of central cytokine, tumor necrosis factor (TNF) involved in inflammation processes become widely investigated in obstetric disorders. Following this the present study is to investigate the effect of TNF-alpha gene G308A (rs1800629) polymorphism on disease risk, renal functions, microvascular permeability, endothelial cell dysfunction and organ involvement in women with preeclampsia. Methods: Initially a 102 3rd trimester pregnant women (preeclamptic-cases and healthy controls) with singleton pregnancy were invited for participation of which 76 were genotyped for TNF-alpha G308A polymorphism, evaluated for plasma levels of sVCAM-1, fibronectin, TNF-alpha and correlated to profile of preeclampsia. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to set association between TNF-apolymorphism and PE risk. For continuous variables we applied Student’s t-test and for categorical variables the Pearson x2 or Fisher’s exact test. The two-way ANOVA with Bonferroni correction was used in multivariate analysis. Results: The A allele was more frequent in cases than controls (22.4% vs. 13.2%) what increased disease risk (OR = 2.73). Maternal serum levels of TNF-alpha, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/mL, 1243 ± 671 ng/mL, 0.308 ± 0.231 g/L) compared to controls (301.1 ± 156.1 pg/mL, 651 ± 250 ng/mL, 0.218 ± 0.101 g/L, p < 0.0001, p < 0.0001, p = 0.031; respectively) and levels shoved increasing trend with mutant allele in genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8% vs. 14.3%, p < 0.05 and 13.0% vs. 4.7%, p < 0.01; respectively). The adverse effect of rs1800629 allele A on renal functions was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study revealed possible association between clinical and laboratory manifestations of preeclampsia and TNF-alpha
gene G308A (rs1800629) polymorphism. This work was supported by the project: ‘‘Centre of excellence for perinatology research (CEPV II)’’, ITMS: 26220120036, co-financed by EU sources (100%). doi:10.1016/j.preghy.2015.07.095
P43. Characterization of monocyte phenotype and polarization in preeclampsia and intrauterine fetal growth restriction Thushari Alahakoon a, Heather Medbury b, Helen Williams b, Nicole Fewings b, Xin Wang b, Vincent Lee⁄ c (a Westmead Hospital, Australia, Department of Obstetrics and Gynecology, Sydney, Australia, b University of Sydney, Sydney Medical School, Sydney, Australia, c Westmead Hospital, Australia, Department of Renal Medicine, Sydney, Australia) Introduction: Monocytes can differentiate into various macrophage phenotypes in health and disease, however the phenotype and polarisation of monocytes in pregnancies complicated by preeclampsia and intrauterine growth retardation has not yet been fully characterised. Objectives: To determine if monocyte phenotype and polarization is altered in pregnancy complications such as preeclampsia and fetal growth restriction. Methods: A prospective cross-sectional case control study. Pregnant women between 24 and 40 weeks of gestation were classified into four clinical groups of Normal pregnancy, Preeclampsia, IUGR and preeclampsia with IUGR (PE+IUGR). The maternal venous blood samples were collected pre-delivery/labour using sterile tubes containing an EDTA salt as the anticoagulant. The samples were analyzed within 2 hours of venipuncture. The whole blood sample was processed for flow cytometry. Staining was performed for expression of surface markers – CD14 used for identification of monocytes, CD16 for classification into monocyte subtypes and CD86 and CD163 for classification into phenotypes M1 and M2. The distribution of maternal monocytes subtypes (classical, intermediate and non classical) were characterized and compared for each clinical group. Results: A total of 54 patients were recruited (normal = 24, PE = 9, IUGR = 12, PE+IUGR = 9). The intermediate monocyte percentage was significantly elevated in IUGR compared to normal pregnancy and in both PE and PE+IUGR for gestations <38 weeks. The level of CD163 expression was significantly increased in the PE+IUGR group for all three monocyte subsets compared to both the controls and PE group, as well as increased on the classical and intermediate subsets for the IUGR compared to PE group. Conclusion: We have shown for the first time that there is a shift towards increased intermediate maternal monocyte subtype in IUGR and PE+IUGR as well as polarization of maternal peripheral monocytes (all subsets) towards M2 in pregnancies complicated by IUGR. These changes may represent the body’s response to and repair of significant placental injury. doi:10.1016/j.preghy.2015.07.096
P44. Syncytiotrophoblast extracellular membrane vesicles from preeclamptic placentae show reduced abilities to guide monocyte maturation and activation as well as reduced activation of cytotoxicity of regulatory T-cells and NK-cells Claudia Göhner a, Jolien Fledderus b, Justine Fitzgerald c, Ekkehard Schleußner c, Udo Markert c, Torsten Plösch a, Sicco Scherjon a, Marijke Faas b (a University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, The