Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population.

INTRODUCTION: Preeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases. OBJECTIVE: The aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE. METHODS: A total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (-308 G→A), IL-10 (-1082 G→A), IL-6 (-174 G→C), and IFN-γ (+874 A→T). Cytokine plasma levels were measured by Cytometric Bead Array method. RESULTS: A higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P<0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P<0.001; P<0.001; P=0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P<0.001; P=0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P<0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively. CONCLUSIONS: These results suggest that IFN-γ seems to play a role in PE occurrence.

Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia.

BACKGROUND: Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-ß1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE. METHODS: Plasma levels of sEng, TGF-ß1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)]. RESULTS: Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-ß1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-ß1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-ß1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. CONCLUSIONS: These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation.

Severe preeclampsia: are hemostatic and inflammatory parameters associated?

BACKGROUND: Preeclampsia (PE) is characterized by hypertension and proteinuria. A predisposition to endothelial dysfunction, which may trigger abnormal activation of the hemostatic and/or inflammatory systems, is thought to play a crucial part in pathogenesis of PE. We investigated the relationship between hemostatic and inflammatory parameters in women with severe PE. METHODS: D-Dimer, PAI-1, IL-8, IL-6, TNF-α, and IFN-γ concentrations were measured in 59 pregnant women with severe PE (sPE), 49 normotensive pregnant and 48 non-pregnant women. RESULTS: D-Dimer and PAI-1 were higher in women with sPE compared to normotensive pregnant and non-pregnant women. IL-8, IL-6, and IFN-γ also were higher in women with sPE compared to normotensive pregnant women. However, only IL-6 and IFN-γ were higher in women with sPE compared to non-pregnant women. Moreover, D-Dimer and PAI-1 showed an elevated area under ROC curve proving to be excellent for discriminating sPE. Correlation analysis showed a weak correlation between D-Dimer and IL-8 and between PAI-1 and IFN-γ in sPE. CONCLUSION: D-Di and PAI-1 concentrations showed to be an important tool for monitoring sPE.

D-dimer in preeclampsia: systematic review and meta-analysis.

Preeclampsia is a multifactorial disease characterized by high blood pressure and proteinuria after the 20th week of pregnancy. Preeclampsia is associated with microvasculature fibrin deposition and maternal organ dysfunction. D-dimer (D-Di) has been used as a marker of production/degradation of fibrin in vivo. D-Di has emerged as a useful diagnostic tool for thrombotic conditions because its plasma concentration has a high negative predictive value for venous thromboembolism. The aim of this study was to evaluate publications that assessed plasma D-Di in preeclampsia and normotensive pregnant subjects to define its diagnostic value. A total of 194 publications were identified. Following the exclusion process, seven studies were in accordance with the pre-defined eligibility criteria. This systematic review was performed with methodologic accuracy, including a careful definition of preeclampsia and a high sensitivity literature search strategy. Quality of the included studies was assessed in accordance with widely accepted literature recommendations. Our meta-analysis indicates that increased plasma D-Di is associated with preeclampsia in the third trimester of gestation vs normotensive pregnant subjects. These preliminary findings in this select group of patients clearly highlight the need for additional comprehensive studies throughout pregnancy, including the establishment of an appropriate cut-off, in order to fully elucidate the diagnostic/prognostic role of D-Di in preeclampsia.