Pre-eclampsia affects cord blood NK cell expression of activation receptors and serum cytokine levels but not CB monocyte characteristics.

PROBLEM: Maternal immunopathology in pre-eclampsia is well studied; however, less is known regarding the immunological effects on the newborns. Increased inflammation and activation of immune cells at the fetal-maternal interface in pre-eclampsia could influence the neonatal immune compartment. METHOD OF STUDY: Monocytes and natural killer (NK) cells from cord blood (CB) of children with pre-eclamptic or healthy mothers were analyzed by flow cytometry for surface markers and intracellular cytokines. In addition, serum cytokine profiles were investigated using ELISA or cytometric bead array. RESULTS: Neonates born to pre-eclamptic mothers had an inflammatory serum cytokine profile. While CB monocyte characteristics seemed unaffected, CB NK cells from pre-eclamptic pregnancies had higher NKp30, but borderline lower NKG2D expression. CONCLUSION: In utero inflammatory priming of neonatal innate immunity taking place in pre-eclamptic pregnancies might influence specific NK cell functions in newborns.

Normalized endothelial function but sustained cardiovascular risk profile 11 years following a pregnancy complicated by preeclampsia.

Women with a history of preeclampsia are at increased risk of future cardiovascular disease. Preeclampsia is associated with elevated blood pressure, inflammation and endothelial dysfunction, and these findings remain 1 year after delivery. Whether these abnormalities persist long after delivery, and whether they may contribute to future cardiovascular disease, is not well studied. We studied 15 women with a history of preeclampsia and 16 matched controls with an uncomplicated pregnancy 11 years following the index pregnancy; all had also been previously examined at 1 year. We assessed arterial stiffness (pulse wave analysis), 24 h ambulatory blood pressure and endothelial function (forearm flow-mediated dilatation and pulse wave analysis following ß receptor agonist provocation), and determined markers of glucose and lipid metabolism, inflammation and vascular function. The preeclampsia group had higher blood pressures and reduced night/day blood pressure ratios, increased body mass index and reduced glucose tolerance, and increased levels of tissue necrosis factor receptor 1 and intracellular adhesion molecule-1, suggesting inflammatory and vascular activation. However, the endothelial impairment observed in the preeclampsia group at 1 year was normalized at 11 years, whereas the control group remained unchanged during follow-up. Our findings of higher blood pressures, impaired glucose tolerance and normalization of endothelial function 11 years after preeclampsia suggest cardiovascular risk factors present already before pregnancy to be more important than permanent endothelial damage for the increased risk of future cardiovascular complications in women with a history of preeclampsia.

Impaired endothelial function and elevated levels of pentraxin 3 in early-onset preeclampsia.

OBJECTIVE: To study endothelial function in relation to anti-angiogenic biomarkers and the inflammatory process in preeclampsia. DESIGN: Observational study. SETTING: Data were obtained from pregnant women who were admitted to the obstetrical ward at the Karolinska University Hospital, Solna, Stockholm, Sweden. POPULATION: Thirty-five women with newly developed and untreated preeclampsia and 30 healthy controls. METHODS: Flow-mediated dilation of the brachial artery, levels of anti-angiogenic and inflammatory markers were measured in plasma during pregnancy and 3-6 months after delivery. Main outcome measures. Flow-mediated dilation of the brachial artery, anti-angiogenic and inflammatory markers. RESULTS: Flow-mediated dilation was decreased in the preeclamptic group at inclusion and at follow-up (p<0.05). Pentraxin 3 (PTX3) and ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) were elevated in women with preeclampsia during pregnancy (p<0.001). Furthermore flow-mediated dilation was lower and the ratio sFlt-1/PlGF and PTX3 were higher in early-onset preeclampsia than late preeclampsia (p=0.018, 0.002 and 0.039). Levels of PTX3 at inclusion correlated inversely with flow-mediated dilation at follow-up both in the preeclampsia and control groups (Spearman, r(s) =-0.47, p=0.02 and r(s) =-0.46, p=0.02 respectively). CONCLUSION: Impaired endothelial function and increased ratio sFlt/PlGF, elevated PTX3 is present in women with preeclampsia and is especially pronounced in women with early-onset preeclampsia.

Women with pre-eclampsia have an altered NKG2A and NKG2C receptor expression on peripheral blood natural killer cells.

PROBLEM: Preeclampsia, a pregnancy disorder, is associated with exaggerated inflammation and increased serum monokines. Uterine natural killer (NK) cells are implicated in preeclampsia pathology, but little is known regarding peripheral NK cells in the disease. METHOD OF STUDY: We examined blood NK cells at delivery in women with preeclampsia, in healthy pregnant women and in healthy non-pregnant blood donors as a reference. RESULTS: Although the percentages of both NKG2A- and NKG2C-positive NK cells were normal in preeclamptic women, the levels of NKG2A and NKG2C on NK cells were significantly up-regulated in these women. In vitro stimulation of PBMCs from healthy pregnant women and blood donors with monokines resulted in increased percentage of NKG2A(+) NK cells and increased NKG2A levels, while levels of NKG2C were decreased. CONCLUSIONS: Our results suggest that the peripheral NK-cell pool is skewed in preeclampsia and possibly under the influence of monokines like interleukin (IL)-15 and IL-12.

Decreased flow-mediated dilation is present 1 year after a pre-eclamptic pregnancy.

OBJECTIVE: Pre-eclamptic toxaemia is associated with inflammation and vascular endothelial dysfunction. As women who have had pre-eclamptic toxaemia are at an increased risk of cardiovascular disease, we hypothesized that these abnormalities are persistent. METHODS: Eighteen women with a history of pre-eclamptic toxaemia and 17 age-matched controls were enrolled. All underwent non-invasive ultrasound examination of the brachial artery for an evaluation of flow-mediated vasodilatation (FMD). The ambulatory blood pressure measurement (ABPM), and plasma concentrations of lipoproteins, inflammation markers, adhesion molecules, glucometabolic and haemostatic factors were determined. RESULTS: Women with a history of pre-eclamptic toxaemia had lower FMD compared with controls (2.5 +/- 2.9 versus 10.3 +/- 2.0%, P < 0.0001). ABPM showed higher systolic, diastolic and mean arterial blood pressures during daytime in the pre-eclamptic toxaemia group than in controls (123 +/- 9, 81 +/- 6 and 95 +/- 6 mmHg versus 116 +/- 9, 76 +/- 7 and 90 +/- 7 mmHg, respectively, all P < 0.05). Among the biochemical determinations, a high value of the homeostasis model assessment of insulin resistance was calculated at 1.3 (1.1-2.1) median [interquartile range (IQR)] in the pre-eclamptic toxaemia group and 1.0 (0.7-1.3) in controls (P < 0.01), and when adjusted for body mass index there was still a significant difference between groups (P < 0.05). No significant differences were found for other metabolic and haemostatic factors. CONCLUSION: Women with a previous history of pre-eclamptic toxaemia have decreased FMD compared with women with a previous normal pregnancy. This perturbation is a proof of an abnormal state still present 1 year after delivery.