Decreased circulating anandamide levels in preeclampsia.

The endocannabinoid system has a key role in female reproduction, including implantation, decidualization and placentation. A growing number of studies indicate that placental and peripheral blood anandamide levels correlate closely with both spontaneous miscarriage and ectopic pregnancy. Anandamide has also been implicated in blood pressure regulation. In this study, we aimed to determine circulating anandamide levels in preeclampsia for the first time in the literature. Forty-three preeclamptic patients and 71 healthy pregnant women were involved in this case-control study. Serum anandamide concentrations were determined by high-performance liquid chromatography-mass spectrometry technique. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, nonparametric methods were applied. Serum levels of anandamide were significantly lower in preeclamptic patients than in healthy pregnant women (0.75 (0.44-1.03) ng ml(-1) vs. 1.30 (0.76-2.0) ng ml(-1), P<0.001). Preeclamptic patients had significantly higher sFlt-1 levels (12,121 (7963-18,316) pg ml(-1) vs. 2299 (1393-3179) pg ml(-1), P<0.001) and significantly lower PlGF concentrations (71.2 (39.2-86.4) pg ml(-1) vs. 256.8 (181.1-421.0) pg ml(-1), P<0.001) as compared with healthy pregnant women. Serum anandamide concentrations did not correlate with serum levels of sFlt-1 and PlGF in our healthy pregnant and preeclamptic groups. In conclusion, we demonstrated for the first time in the literature that serum anandamide concentrations are decreased in women with preeclampsia. However, the cause and consequence of this observation remain to be determined.

Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome.

The HSD11B1 gene encodes the type 1 isoform of the 11-ß-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.

Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study.

BACKGROUND: Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. METHODS: Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF≥100 pg/ml), low (12

Changes in exhaled breath condensate pH in healthy and asthmatic pregnant women.

OBJECTIVE: Asthma is a common chronic disease complicating pregnancy with a risk for perinatal complications. Control of airway inflammation in the asthmatic pregnancy improves pregnancy outcomes. Our aim was to evaluate pH of exhaled breath condensate (EBC), a non-invasive method for the assessment of asthmatic airway inflammation, in healthy and asthmatic pregnancies. DESIGN: Cross-sectional study. SETTING: Hungarian university clinics. POPULATION: Seventeen healthy pregnant women, 21 asthmatic pregnant women, 23 healthy non-pregnant women and 22 asthmatic non-pregnant women. METHODS: EBC samples were collected using a portable condenser, EBC pH was measured after argon deaeration. MAIN OUTCOME MEASURE: EBC pH. RESULTS: EBC pH (mean ± SD) of healthy non-pregnant and asthmatic non-pregnant women was similar (7.75 ± 0.27 vs. 7.54 ± 0.57; p = 0.118), probably indicating an optimal control of airway inflammation in asthmatic women. On the other hand, EBC pH was higher in healthy pregnant women compared with healthy non-pregnant women (8.02 ± 0.43 vs. 7.75 ± 0.27; p = 0.017). Higher EBC pH accompanying healthy pregnancy was absent in asthmatic pregnant patients whose EBC pH was lower (7.65 ± 0.38) than that of healthy pregnant women (p = 0.006), and it was similar to that in asthmatic and healthy non-pregnant women (p = 0.470 and p = 0.300, respectively). The EBC pH in asthmatic pregnant women correlated positively with birthweight (r = 0.49, p = 0.047) and negatively with forced vital capacity (r = 0.45, p = 0.039). EBC pH was not related to blood pH. CONCLUSIONS: EBC pH is higher in healthy pregnant women but not in asthmatic pregnant women compared with data from healthy non-pregnant women, indicating that oxidative inflammatory processes induced by asthma may compromise the regulatory mechanisms causing alkaline pH in the airways during pregnancy.

Evaluation of a rapid and simple placental growth factor test in hypertensive disorders of pregnancy.

The aim of this study was to investigate the diagnostic accuracy of the Triage placental growth factor (PlGF) assay, together with its prognostic efficiency in determining the need for preterm delivery in all forms of hypertensive disorders of pregnancy. A total of 130 pregnant women with a diagnosis of preeclampsia (PE: 23), HELLP syndrome (20), superimposed preeclampsia (SIPE: 17), chronic hypertension (CHT: 25), gestational hypertension (GHT: 18) and 27 normotensive pregnant controls were enrolled in this case-control study. A single blood sample was taken between 22 and 34 weeks of gestation, and the plasma was analyzed for PlGF using the Alere Triage PlGF assay. The PlGF levels found in all hypertensive disorder groups differed significantly from those observed in controls. There was a highly significant difference in PlGF concentrations between women with a pregnancy duration <35 weeks and controls. Using a gestational age-dependent threshold of 5% of normal, a positive PlGF test predicted delivery before 35 weeks in 93.7% of hypertensive women and delivery before 37 weeks in 90.5% of hypertensive women. A positive PlGF test identified the following proportions of hypertensive patients: 95.7% (PE), 95.0% (HELLP syndrome), 82.4% (SIPE), 60.0% (CHT) and 44.4% (GHT). A positive PlGF test was associated with a significantly shorter duration of pregnancy (hazard ratio of 3.43 adjusted for the gestational age at the time of sample collection and hypertension with proteinuria). In conclusion, PlGF concentrations are significantly lower in all hypertensive disorders. A positive test using the Triage PlGF assay at 22-34 weeks of gestation predicts delivery before 37 weeks in women with both proteinuric and non-proteinuric hypertensive disorders of pregnancy.

Prevalence of intracellular galectin-1-expressing lymphocytes in umbilical cord blood in comparison with adult peripheral blood.

Umbilical cord blood (UCB) is a promising alternative for the treatment of hematological malignancies. The lower immune reactivity of UCB lymphocytes is a well-known phenomenon; however, immune tolerance mechanisms are not fully elucidated. Galectin-1 has strong immunosuppressive properties and plays a key role in the regulation of immune reactivity. We aimed to determine the properties of intracellular galectin-1 (Gal-1)-producing cells within CD3, CD4, CD8, regulatory T (Treg), and natural killer (NK) cells in UCB compared to adult peripheral blood (APB). We took peripheral blood samples from 22 healthy adults and cord blood samples from 19 healthy, term neonates. Intracellular Gal-1 expression was determined by flow cytometry in the above subsets. Furthermore, we assessed the prevalence of naive and memory T cells that play a role in the regulation of immune reactivity. We also performed functional analyses to assess the effect of exogenous Gal-1 on the rate of proliferation of T lymphocytes isolated from APB and UCB. The prevalence of intracellular Gal-1-expressing CD3, CD4, CD8, Treg and NK lymphocytes was lower in UCB than in APB. However, their capability to produce Gal-1 reaches the level seen in adults. The prevalence of naive cells was higher, whereas that of central and effector memory T cells was lower in UCB compared with APB. Lower Gal-1-producing cell proportion might be due to the naivety of neonatal lymphocytes, as indicated by the positive correlation detected between the number of CD3 lymphocytes expressing intracellular Gal-1 and the prevalence of memory T cells. The intracellular expression of Gal-1 may be down-regulated in neonatal lymphocytes due to the already reduced immune reactivity of UCB. In contrast with previous findings, our results indicate that the administration of exogenous Gal-1 failed to decrease the rate of proliferation in T lymphocytes isolated from either APB or UCB. This suggests that Gal-1-expressing lymphocytes are unlikely to play a major role in mitigating the immune reactivity of UCB.

Early prenatal detection of a fast-growing fetal epignathus.

Epignathus is a rare congenital orofacial teratoma. We present a case of a fast-growing tumor, where early prenatal diagnosis was made and where fetopathological examination revealed the reason of the remarkable ultrasonographic signs and underlined the expected poor prognosis. Ultrasonographic examination at 18 weeks' gestation showed that there was a growing tumor protruding from the fetus's mouth. The fetal stomach could not be seen and extreme polyhydramnios was also detected. After counseling, the couple opted for a termination of pregnancy. Fetopathological examination showed that the tumorosus mass was not only protruding from the mouth, but also inexplicably grew downwards, was connected to the hard palate and the periosteum of the vertebral corpus, making an airway and esophageal obstruction, causing the ultrasonographic findings. Postnatal treatment and surgical removal of this tumor seemed to be impossible. In case of an early detection of a fast-growing fetal epignathus, pregnancy termination should be considered.

Circulating levels of thrombospondin-1 are decreased in HELLP syndrome.

BACKGROUND: Preeclampsia is characterised by an imbalance of circulating pro- and anti-angiogenic factors. The syndrome of haemolysis, elevated liver enzymes and low platelet count (HELLP) develops mostly on the ground of preeclampsia, and one of its important features is the severe disturbance of the coagulation system, intravascular coagulopathy. Thrombospondin-1 (TSP-1) is derived from the endothelium and platelets, and exerts potent pro-thrombotic and anti-angiogenic effects. Our aim was to determine, whether its circulating levels are altered in preeclampsia and in HELLP syndrome. METHODS: We enrolled 45 pregnant women with early-, 43 with late-onset preeclampsia, 21 with HELLP-syndrome, 45 with uncomplicated pregnancy and 20 non-pregnant controls in our case-control study. TSP-1 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Circulating TSP-1 levels were lower in HELLP syndrome compared to all other study groups, while they were unaltered in preeclampsia compared to the control groups. There was a significant positive linear correlation between TSP-1 levels and platelet count in HELLP syndrome. In patients with more severe HELLP syndrome, TSP-1 levels were significantly lower compared to women suffering from a milder form of HELLP syndrome. CONCLUSIONS: Circulating thrombospondin-1 levels are decreased in HELLP syndrome and they seem to reflect disease severity, lower levels representing a more severe state. Nevertheless, despite its potent anti-angiogenic effect, our results suggest that circulating TSP-1 does not play a significant role in the pathogenesis of preeclampsia.

Peripheral T(h)1/T(h)2/T(h)17/regulatory T-cell balance in asthmatic pregnancy.

Asthma is a common chronic disease that may complicate pregnancy and a risk factor for complications; however, immunological mechanisms of the bilateral interactions between asthma and pregnancy are not fully understood. Healthy gestation is characterized by a sensitive balance of T(h)1/T(h)2/T(h)17/regulatory T (Treg) cells that may be altered in asthmatic pregnancy. The aim of this study was to describe the prevalence of these cell subsets in asthmatic compared with healthy pregnancy. The prevalence of T(h)1, T(h)2, T(h)17 and Treg lymphocytes was identified by cell surface and intracellular marker staining in blood samples of 24 healthy non-pregnant (HNP), 23 healthy pregnant (HP), 15 asthmatic non-pregnant (ANP) and 15 asthmatic pregnant (AP) women using flow cytometry. The T(h)1/T(h)2 cell ratio was decreased in both HP and ANP compared with HNP women; however, no further decrease was observed in the AP group. The T(h)17/Treg ratio was decreased in HP, but not in AP women, compared with HNP data. Healthy pregnancy increased Treg cell prevalence compared with HNP data (4.64% versus 2.98%; P < 0.05), and this pregnancy-induced elevation was absent in AP women (2.52% versus 4.64%; P < 0.05). T(h)17 cell prevalence was similar in the HP and HNP groups (2.78% versus 3.17%; P > 0.05). Asthma increased T(h)17 prevalence in non-pregnant patients (3.81% versus 3.17%; P < 0.05), and this asthma-specific increase of T(h)17 cell prevalence was also observed in AP patients (AP versus HP: 3.44% versus 2.78%; P < 0.05). The abnormal asthma-dependent T(h)17 elevation together with blunted Treg increase may play a role in the compromised immune tolerance characterizing asthmatic pregnancy.

Increased prevalence of peripheral blood granulysin-producing cytotoxic T lymphocytes in preeclampsia.

Preeclampsia (PE) is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Granulysin is a cytolytic and pro-inflammatory molecule expressed by activated human cytotoxic T lymphocytes and natural killer (NK) cells. Recent data show that serum granulysin levels are elevated in preeclampsia. The purpose of this study was to determine whether the proportion of peripheral blood cytotoxic T lymphocytes and NK cells that express intracellular granulysin is altered in PE. Twenty-two preeclamptic patients and 29 healthy pregnant women were involved in this case-control study. Intracellular granulysin expression of lymphocytes was determined with flow cytometric examination. In healthy pregnant women, the majority of NK cells and a small fraction of cytotoxic T cells expressed granulysin in their cytoplasma (median (25-75 percentile): 53.5 (45.6-68.0)% and 13.8 (8.5-23.1)%, respectively). In PE, the percentage of granulysin-positive cytotoxic T lymphocytes was markedly increased, while the proportion of granulysin-producing NK cells was unchanged as compared to healthy pregnant women (for cytotoxic T cells: 34.1 (19.3-45.6)%, p<0.001; for NK cells: 57.2 (42.9-74.9)%, p>0.05). Maternal age of healthy pregnant women showed a significant inverse correlation with the frequency of granulysin-expressing NK cells (Spearman R=-0.44, p<0.05), while their BMI correlated positively with the proportions of granulysin-positive cytotoxic T cells and NK cells (Spearman R=0.43, p<0.05 for both). In conclusion, the majority of circulating NK cells but only a small population of cytotoxic T cells shows intracellular granulysin expression in normal pregnancy. In preeclampsia, the proportion of granulysin-producing cytotoxic T cells in the peripheral blood is markedly increased, which might contribute to the development of the pro-inflammatory Th1-type immune responses characteristics of the maternal syndrome of the disease.

Soluble urokinase plasminogen activator receptor (suPAR) levels in healthy pregnancy and preeclampsia.

BACKGROUND: Preeclampsia is characterized by a maternal systemic inflammatory response and the impairment of maternal immune tolerance present in healthy pregnancy. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the monitoring of systemic inflammation. We aimed to assess the levels of suPAR and other markers of systemic inflammation in preeclampsia compared to healthy pregnancy. METHODS: We determined plasma suPAR, IL-6 and high sensitivity C-reactive protein (hs-CRP) levels in plasma samples of 62 healthy pregnant and 41 preeclamptic women in the third trimester of pregnancy. RESULTS: Plasma suPAR levels were elevated in preeclampsia [3.18 (2.30-4.71) ng/mL vs. 2.02 (1.81-2.40) ng/mL, p=0.0001, median (interquartile range)]. IL-6 and hs-CRP levels were also higher compared with healthy pregnancy [5.99 (2.97-18.12) pg/mL vs. 1.41 (1.00-2.70) pg/mL, p=0.0001 and 6.60 (3.55-15.40) mg/L vs. 3.90 (2.10-7.25) mg/L, p=0.006, respectively, median (interquartile range)]. Linear regression analyses revealed an association between individual plasma suPAR and log IL-6 levels as well as log hs-CRP levels. CONCLUSIONS: suPAR levels are elevated in preeclampsia and vary in a narrower range compared with IL-6 and hs-CRP. ROC analysis indicated that monitoring of suPAR levels is a suitable tool for the detection of systemic inflammation in pregnancy.

Circulating levels of the anti-angiogenic thrombospondin 2 are elevated in pre-eclampsia.

An imbalance of maternal circulating pro- and anti-angiogenic factors may play a role in the pathogenesis of pre-eclampsia. Thrombospondin 2 (TSP-2) is a protein expressed mainly by activated endothelial cells, which acts as a potent anti-angiogenic agent. Our aim was to determine whether serum TSP-2 levels are altered in pre-eclampsia. We enrolled 35 pre-eclamptic patients and 35 healthy pregnant women in the study. Thrombospondin 2 levels were determined by enzyme-linked immunosorbent assay, while soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations were determined by electrochemiluminescence immunoassay. In patients with PE, we demonstrated 1.7-fold higher TSP-2 [13.2 (9.4-18.1) vs. 7.9 (7.2-11.2) ng/ml, p<0.001], 3.8-fold higher sFlt-1 and 4.3-fold lower PlGF levels compared with the control group. There were no associations between TSP-2 and sFlt-1 or PlGF concentrations. We suggest that circulating TSP-2 levels may contribute to the pathogenesis of PE via its anti-angiogenic properties, but in a distinct way from sFlt-1 and PlGF.

Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia.

BACKGROUND: There is a variable tandem repeat polymorphism in the 5'-flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension. Our aim was to identify this polymorphism in samples of pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations. METHODS: Blood samples were collected from healthy pregnant normotensive women (n=235) and women with pre-eclampsia (n=220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The plasma BNP concentration was measured by fluorescence immunoassay method. RESULTS: We detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The number of 10-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnant controls (p=0.032). After adjustment for confounding factors pre-pregnancy BMI, maternal age, primiparity and smoking, the calculated odds ratio (OR) was 0.19 (95% CI: 0.04-0.87). Similarly, the 12-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnants (p=0.037; adjusted OR: 0.53 (95% CI: 0.29-0.96)). In contrast the 11-repeat genotype carrier frequency was significantly higher in the pre-eclamptic than in the healthy pregnant group (p<0.001; adjusted OR 2.91 (95% CI: 1.75-4.84)). The concentration of the BNP was 9.75pg/ml in the healthy controls and 32.40pg/ml in the pre-eclamptic group (p<0.0001). The 11/11 genotype carriers had significantly higher BNP levels in both groups. CONCLUSIONS: The NPPB gene (TTTC) microsatellite polymorphism in the 5'-flanking region showed significant difference in the distribution of alleles and genotypes between healthy pregnant controls and pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in pre-eclamptic women, and it showed association with the (TTTC) genotypes. We introduced an F-PCR and DNA fragment analysis method for the fast and reliable detection of this STR.

Peripheral blood galectin-1-expressing T and natural killer cells in normal pregnancy and preeclampsia.

The purpose of this study was to determine whether the proportion of galectin-1-expressing peripheral blood T and NK cells is altered in normal pregnancy and preeclampsia (PE). We also examined whether circulating levels of galectin-1 and anti-galectin-1 autoantibodies are affected in PE. Seventy preeclamptic patients, 75 healthy pregnant and 21 healthy non-pregnant women were involved in this study. Serum galectin-1 and anti-galectin-1 autoantibody levels were measured by ELISA. Intracellular galectin-1 expression of lymphocytes was determined with flow cytometry. Serum galectin-1 and anti-galectin-1 IgG levels did not differ significantly between the healthy pregnant and the PE group. In healthy pregnant women, significantly higher percentage of T and NK cells expressed gal-1 in their cytoplasma than in healthy non-pregnant women. However, the proportion of galectin-1-expressing peripheral blood T and NK cells was markedly decreased in PE compared to normal pregnancy, which might contribute to the activation of innate and acquired immune cells.

Increased prevalence of IL-17-producing peripheral blood lymphocytes in pre-eclampsia.

PROBLEM: Systemic inflammation is a dominant component in the pathogenesis of pre-eclampsia. Besides the imbalance of Th1 and Th2 cells, alterations of the prevalence of Th17 and regulatory T cells have also been suggested to contribute to inflammation. We aimed to describe the prevalence of these four CD4 lymphocyte subtypes in pre-eclampsia and normal pregnancy, along with that of IL-17-producing CD8 and NK cells. METHOD OF STUDY: Twenty pre-eclamptic and 22 normal pregnant women were enrolled in this study. Using flow cytometry, we determined the prevalence of IL-17-producing cells among the CD4, CD8 and NK cell subsets. Furthermore, we measured the prevalence of CD4+ Tregs, and Th1/Th2 cells were characterized using cell surface chemokine receptor markers. RESULTS: We demonstrated that there is a shift not only in the Th1/Th2 but also in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in pre-eclampsia. The proportion of CD8 and NK cells that express IL-17 was also higher in pre-eclampsia. CONCLUSION: The prevalence of IL-17-producing CD4, CD8 and NK cells is elevated in pre-eclampsia, indicating that both the innate and adaptive arms of the immune system are involved in the development of the exaggerated maternal systemic inflammation observed in this pregnancy-specific disorder.

Lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in healthy pregnancy and preeclampsia.

PROBLEM: Calcium handling of T lymphocytes is altered in healthy pregnancy (HP) and preeclampsia (PE) compared to non-pregnant (non-P) women. We compared the activation-elicited calcium influx in T lymphocytes in HP, PE and non-P women and tested its alteration upon inhibition of Kv1.3 and IKCa1 potassium channels. METHOD OF STUDY: The alteration of calcium influx was measured in major T-lymphocyte subsets of 9 non-P, HP and PE women with flow cytometry with or without treatment of cells with potassium channel inhibitors. RESULTS: The elicited calcium response was lower in HP compared to non-P. In HP, calcium influx was sensitive to potassium channel inhibition in CD8 and Th1, but not in Th2 cells. In PE, calcium influx and its sensitivity to inhibition were comparable to non-P. CONCLUSION: There is a characteristic pattern of calcium influx in T lymphocytes and its sensitivity to potassium channel inhibition in HP that is missing in PE, raising the notion that T-lymphocyte calcium handling may have a role in the characteristic immune status of HP.

Decreased proportion of peripheral blood vascular endothelial growth factor-expressing T and natural killer cells in preeclampsia.

OBJECTIVE: The purpose of this study was to determine the proportion of circulating T and natural killer (NK) cells that express intracellular vascular endothelial growth factor (VEGF) in women with preeclampsia compared to those with a normal pregnancy. STUDY DESIGN: In all, 24 preeclamptic patients and 30 healthy pregnant women were involved in this case-control study. Intracellular VEGF expression of unstimulated lymphocytes was determined with flow cytometric examination. RESULTS: In healthy pregnant women, the majority of both T and NK cells expressed VEGF in their cytoplasma (median, 79.9%; 25-75 percentile, 73.7-87.0 and median, 78.3%; 25-75 percentile, 64.1-85.3, respectively). Furthermore, CD4(+) helper and CD8(+) cytotoxic T cells showed a similar pattern of VEGF expression in normal pregnancy. However, the proportion of VEGF-expressing peripheral blood T (both helper and cytotoxic) and NK cells was markedly decreased in preeclampsia (for T cells: median, 51.6%; 25-75 percentile, 40.1-60.0; P < .001; for NK cells: median, 45.2%; 25-75 percentile, 27.4-64.0; P < .001). CONCLUSION: Our results suggest decreased production of VEGF by circulating T and NK cells in preeclampsia, which might contribute to the development of the generalized endothelial dysfunction characteristic of the maternal syndrome of the disease.

Hepcidin concentrations and iron homeostasis in preeclampsia.

BACKGROUND: Plasma iron is increased in preeclampsia (PE) when compared to healthy pregnant women. This is in contrast to inflammation characteristic for PE. The link between iron homeostasis and inflammation is hepcidin. Our goal was to describe hepcidin concentrations and its association with iron homeostasis in PE. METHODS: We obtained peripheral blood samples from 30 preeclamptic [gestational age: 36.5 (24-40) weeks] and 37 healthy pregnant women [gestational age: 36 (28-39) weeks] to determine plasma hepcidin and interleukin-6 (IL-6) concentrations, complete blood cell counts and parameters of iron homeostasis [plasma iron, transferrin and ferritin levels and total iron binding capacity (TIBC)]. Hepcidin was measured using mass spectrophotometry. The Mann-Whitney test was used for statistical analysis. RESULTS: Plasma hepcidin, IL-6, iron and ferritin concentrations were increased (p<0.05 for all), whereas plasma transferrin, TIBC and mean corpuscular hemoglobin concentrations were lower (p<0.05 for all) in PE compared to healthy pregnant women. No differences were seen in the other parameters investigated. CONCLUSIONS: Plasma iron concentrations are increased despite high hepcidin concentrations in PE. This might indicate a resistance to the iron-decreasing action of hepcidin.

Effector and regulatory lymphocytes in asthmatic pregnant women.

PROBLEM: Asthma influences pregnancy outcome and pregnancy affects asthma severity, but the immunologic mechanisms of these interactions are not fully elucidated. METHOD: The prevalence of lymphocyte subsets was identified by cell surface markers and intracellular FoxP3 staining, in healthy non-pregnant (HNP; N = 15), healthy pregnant (HP; N=33), asthmatic non-pregnant (ANP; N=62) and asthmatic pregnant (AP; N=61) women. RESULTS: Regulatory T cell (Treg) prevalence was higher in HP than in HNP subjects and showed a positive correlation with fetal birth weight, which was blunted in AP group. Treg prevalence was lower and invariable natural killer T cell prevalence was higher in AP patients (compared to HP). Higher naive and lower effector T cell prevalence was observed in AP than in ANP group. CONCLUSION: Pregnancy-induced increase in Treg cell prevalence is absent in asthmatic pregnancy that may interfere with physiological intrauterine growth. However, pregnancy-specific inhibition of asthmatic inflammation can be detected in uncomplicated asthmatic pregnancy.