Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation

The aim of this study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+), BDCA-4(+)) and the CD1c(+):BDCA-2(+) ratio in phases of the ovarian cycle and in normal pregnant patients. 18 non-pregnant women and 17 normal pregnant women were included. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies (mAbs) against blood dendritic cell antigens (anti-BDCA-1, BDCA-2, BDCA-4) and estimated using flow cytometry. CD1c(+), BDCA-2(+) and BDCA-4(+) dendritic cells were present in the follicular and luteal phases of the ovarian cycle and in all trimesters of normal pregnancy. The percentages of CD1c(+) dendritic cells did not differ between the follicular and luteal phases of the ovarian cycle. The percentage of BDCA-2(+) dendritic cells was lower in the luteal phase of the ovarian cycle compared with the follicular phase, but the differences were not statistically significant. The CD1c(+):BDCA-2(+) cell ratio was significantly lower in the luteal phase compared with the follicular phase of the ovarian cycle. The numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, the CD1c(+):BDCA-2(+) ratio was higher than in the other trimesters of normal pregnancy. All populations of dendritic cells and the CD1c(+):BDCA-2(+) ratio did not differ in the first and third trimesters of physiological pregnancy. Our results suggest that myeloid and lymphoid dendritic cells are not affected by steroid hormones during the menstrual cycle. The deficiency of peripheral blood dendritic cells observed during the second trimester of normal pregnancy can be associated with their migration to the uterus during the second physiological invasion by cytotrophoblast.     

Autologous mixed lymphocyte reaction (AMLR) in man. XVI. The AMLR and monoclonal antibody-defined T cell subsets and HNK 1+ natural killer cells in normal human pregnancy

Peripheral blood mononuclear cells from 27 pregnant women and 10 age-matched non-pregnant women were examined for monoclonal antibody-defined T cells, immunoregulatory T-cell subsets, natural killer cells, activated T cells and surface Ig+B lymphocytes using a fluorescence-activated cell sorter (FACS analyzer). The autologous mixed lymphocyte reaction (AMLR) and in vitro influence of interleukin 1 (IL-1) and interleukin 2 (IL-2) on the AMLR were also studied. No significant difference was observed in the proportions of Leu 3+ (helper/inducer phenotype) and Leu 2+ (suppressor/cytotoxic) T cells during all three trimesters of pregnancy and in post-partum period when compared to non-pregnant healthy control women. T cells expressing DR antigen (evidence of T-cell activation) were significantly increased during second trimester (P less than 0.02) and in post-partum period (P less than 0.05). However, Tac+ T cells (IL-2 receptor positive T cells, another but distinct marker for T cell activation) were normal throughout pregnancy and in the post-partum period. Leu 7+ (HNK 1+) lymphoid cells (containing a population of natural killer cells) were normal during all 3 trimesters of pregnancy but were increased during post-partum period. Surface Ig+B cells were comparable to control group throughout pregnancy and during post-partum period. The AMLR was significantly deficient (P less than 0.01) during first and third trimester of pregnancy. In vitro addition of purified IL-2 restored the AMLR to the baseline levels of the controls but the AMLR was still lower than the levels in controls with IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)     

正常妊娠和子痫前期患者外周血树突细胞亚群的变化

目的:探讨树突细胞(DCs)及其亚群在正常妊娠和子痫前期患者间的变化,及与Th1/Th2型反应的关系。方法:选取正常妊娠孕妇25例、子痫前期患者17例和正常未孕妇女15例,用流式细胞术检测3组外周血树突细胞及其髓样(MDC)和淋巴样(PDC)亚群,比较其数量和比值在妊娠前后及子痫前期患者的变化,并与Th1/Th2型细胞因子的含量比较。结果:与正常妊娠早期和晚期相比,妊娠中期MDC和PDC数量减少,MDC/PDC比值升高,妊娠早、晚期相比无显著差异。与正常晚期妊娠妇女比较,子痫前期患者PDC数量减少,MDC数量改变不明显,MDC/PDC比值升高,两组相比差异显著。与正常晚期妊娠妇女相比较,子痫前期患者Th1型细胞因子IL-2含量增加,IFN-γ无显著差异,Th2型细胞因子IL-10减少,IL-2/IL-10、IFN-γ/IL-10比值升高。结论:DCs在正常妊娠的不同阶段其数量和亚群发生变化,子痫前期患者出现PDC减少和MDC/PDC比值升高现象,并与Th1/Th2型细胞因子的变化趋势一致。     

Pregnancy-associated changes in peripheral blood lymphocyte subpopulations in normal Kuwaiti women.

It has recently been reported that healthy pregnancy is associated with systemic immunosuppression. The aim of this study was to evaluate the numbers and distribution of lymphocyte subpopulations in normal, healthy pregnant Kuwaiti women. Thirty-four healthy normotensive women in the 3rd trimester of pregnancy were studied using flow cytometry to define lymphocyte subpopulations and were compared with 16 non-pregnant women. A decrease in the absolute numbers of lymphocytes was observed affecting T cells (CD3+, CD4+, CD8+), B cells (CD19+), and natural killer cells (CD16+/CD56+). When analyzed as a percentage of the total lymphocyte population, there was a significant decrease in B cells and an increase in CD4+ T cells. The T cell population revealed increased expression of CD25 on CD4+ and CD8+ cells, of HLA-DR on CD8+ cells, and of CD54 on CD4+ T cells. The reduced number of lymphocytes suggests that Kuwaiti females may be immunosuppressed in the 3rd trimester of pregnancy. The presence of activated CD4+ T cells could indicate the expression of a regulatory suppressor T cell population, as Treg cells are CD4+CD25+, and suppressor T cells are thought to be CD8+. Future work is required to explore the significance of these T cell populations in pregnancy.     

Immunological changes in normal pregnancy.

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.     

Lymphoid and myeloid cell populations in the non-pregnant human Fallopian tube and in ectopic pregnancy

Lymphoid and myeloid cell populations in human endometrium are well-documented and are known to play important roles in providing immune tolerance, controlling trophoblast invasion, and mediating vascular remodeling. Immune cell populations in the Fallopian tube have not been comprehensively studied. The aim of this study was to characterize lymphoid and myeloid cell populations in non-pregnant Fallopian tube and determine whether they are altered in Fallopian tube from women with ectopic pregnancy. Fallopian tube was analyzed by flow cytometry and immunohistochemistry. Populations of CD3+ (CD4+ and CD8+) lymphocytes, LIN1-HLADR+ (CD123+ and CD11c+) dendritic cells, monocytes, neutrophils, and CD56(dim)CD16- natural killer (NK) cells were demonstrated to be present in non-pregnant Fallopian tube. CD123+ dendritic cells were predominant over CD11c+ dendritic cells. Numbers of CD11c+ cells were significantly higher in the progesterone-dominant mid-luteal phase of the menstrual cycle compared with the follicular phase. Numbers of CD45+ leukocytes, CD68+ cells, and CD11c+ cells were higher in Fallopian tube from women with ectopic pregnancy compared with mid-luteal phase Fallopian tube. These data will advance our understanding of normal human Fallopian tube physiology and disorders of Fallopian tube function, such as ectopic pregnancy.     

Immunosuppressive effect of pregnant mouse serum on allostimulatory activity of dendritic cells

In normal pregnancy, the maternal immune system is directed towards tolerance or suppression in order to prevent rejection of the semi-allogenic fetus. Antigen-presenting cells, especially dendritic cells (DCs), are key cells in initiation and regulation of immune responses. The presence of potent immunostimulatory DCs in the decidual tissue of pregnancy has been demonstrated. The aim of this study was to determine how allostimulatory activity of DCs could be affected during pregnancy. DCs were isolated from spleen of pregnant or non-pregnant Balb/c mice and co-cultured with allogenic T lymphocytes prepared from brachial lymph nodes of C57BL/6 mice. Some cultures of non-pregnant female DCs were treated by 2.5% serum obtained from pregnant mice at early, middle or late gestational periods, and were used in the same mixed lymphocyte reaction (MLR) settings. Cell proliferation was measured by 3H-thymidine incorporation, and cytokine production measured in supernatants of MLR cultures using ELISA. The effect of pregnant mouse serum on expression of DC surface markers was evaluated by flow cytometry. No significant difference was found between stimulatory potential of splenic DCs from pregnant and non-pregnant mice in induction of allogenic T cell proliferative response. Moreover, serum of early or late pregnancy did not have any effect on DC function in comparison with non-pregnant mouse serum, while mid-pregnancy serum significantly inhibited allostimulatory activity of DCs. IFNgamma production in co-culture of DCs treated with pregnant mouse serum was significantly lower than that of the control group; however, no significant difference in IL-10 production was observed. Treatment of DCs with pregnant mouse serum did not influence the percentage of cells expressing MHC-II, CD86, CD8alpha or CD11b. However, a marked reduction of the mean fluorescence intensity of MHC-II was observed. Collectively, our results concerning the diminished capacity of DCs to induce production of Th1 cytokines and allogenic T cell proliferation after treatment with pregnant mouse serum reveal a new way of immunologic tolerance against the semi-allogenic fetus.     

The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia

The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.     

妊娠中晚期外周血T淋巴细胞亚群和NK细胞的观察

目的 :检测孕妇外周血T淋巴细胞亚群和NK细胞的变化 ,探讨正常妊娠时母体的细胞免疫状态。方法 :健康孕妇 92例按孕周分为 3组 :中孕组 (孕周 13～ 2 7+ 6周 )、晚孕未足月组 (孕周 2 8～ 36 + 6周 )和足月组 (孕周 37～ 4 1+ 6周 ) ;另取同期健康未孕生育年龄妇女 2 0例作对照组。用流式细胞仪检测其外周血T淋巴细胞亚群和NK细胞的相对数 ,结合外周血白细胞计数计算其绝对数。结果 :正常孕妇外周血白细胞总数显著增加 ,其中粒细胞百分数和绝对数均显著增加 ,单核细胞绝对数增加 ,淋巴细胞百分数和绝对数均显著减少 ;CD3+ 细胞百分数显著增加 ,CD4 + 细胞百分数和绝对数均显著减少 ,CD4 + /CD8+ 比值显著下降 ,CD8+ 细胞差异无显著性 ;NK细胞百分数和绝对数均显著减少。随着孕周进展 ,CD4 + 细胞百分数和绝对数均逐渐减少 ,CD4 + /CD8+ 比值逐渐下降 ,中孕组与晚孕未足月组比较 ,差异有显著性 (P <0 .0 5 )。结论 :妊娠期母体细胞免疫功能处于免疫抑制状态 ;随着妊娠进展 ,这种抑制有一定程度的下降。     

CD4(+)CD25+ T regulatory cells in murine pregnancy

Mammalian pregnancy is thought to be a state of immunological tolerance and immunological pregnancy complications may result from incomplete allo-tolerance. We reported recently a higher frequency of Th1 cytokine-producing T cells specific against paternal antigens in abortion-prone mice compared to normal pregnant mice. Since Th2 cells were shown to be not essential for normal pregnancy; alloreactive Th1 cells must be differently regulated. In this context, T regulatory cells (Treg) were proposed to play an essential role. Normal pregnant mice show an expansion of CD4(+)CD25+ and IL-10+ Treg cells at the periphery compared to non-pregnant animals. Further, we reported significantly lower frequencies of Treg in abortion-prone mice. Interestingly, CD4(+)CD25+ Treg cells from normal pregnant mice were able to prevent fetal rejection. Accordingly, down-regulated levels of Treg were also reported during human miscarriage. The putative mechanisms involved in Treg-induced tolerance in mice and humans are discussed in this review.     

Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy

Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.     

The ratio of interleukin (IL)-18 to IL-12 secreted by peripheral blood mononuclear cells is increased in normal pregnant subjects and decreased in pre-eclamptic patients

Interleukin (IL)-18 acts in synergy with IL-12 to promote development of T helper 1 (Th1) responses. On the other hand, IL-18 alone has the capacity to induce Th2 responses. Here, we have measured IL-18 and IL-12 secretion by non-stimulated peripheral blood mononuclear cells (PBMC) from 17 non-pregnant women, 21 healthy pregnant women, 9 mildly pre-eclamptic patients and 15 severely pre-eclamptic patients. Th1/Th2 ratios in PBMC were determined by flow cytometry. PBMC from healthy pregnant subjects secreted more IL-18 and less IL-12 than non-pregnant women. PBMC from severely pre-eclamptic patients secreted more IL-12 than those from healthy pregnant women, while IL-18 secretion in mildly pre-eclamptic patients resembled that in normal pregnancy. The ratios of IL-18 to IL-12 were significantly higher in healthy pregnant women than non-pregnant women. These ratios were significantly lower in severely pre-eclamptic cases than in normal pregnancy subjects, while these ratios in mild pre-eclampsia resembled those in normal pregnancy. Interestingly, Th1/Th2 ratios were negatively correlated with the ratios of IL-18/IL-12. These results suggest that elevated IL-18 secretion and decreased IL-12 secretion by PBMC may induce Th2 dominance in normal pregnancy, while elevated secretion of both IL-18 and IL-12 by PBMC may cause Th1 dominance in severe pre-eclampsia.     

Leucocyte counts in pregnant Nigerian women with sickle cell trait

White blood count (WBC) with differential counts and packed cell volume (PCV) were studied in 100 pregnant and 30 non-pregnant control women aged 18-45 years. Eighty of the pregnant women were homozygous HbAA and 20 heterozygous HbAS. The non-pregnant women's PCV, lymphocyte and eosinophils counts were significantly higher (p < 0.005) while their leucocytes neutrophil counts were significantly lower (p < 0.005) compared with HbAA and HbAS pregnant women. However, HbAS pregnant women had higher leucocyte, lymphocyte and eosinophil counts compared with HbAA, but these were not significant. There were no variations in basophil and monocyte counts. HbAA pregnant women had no change in PCV but significant changes occurred in leucocyte and neurophil counts with increase in the second trimester with decreasing lymphocyte and eosinophil counts in the second and third trimesters. However, HbAS pregnant women had significant increase in PCV in their first trimester, leucocyte and neutrophil counts in their third trimester but no variation in lymphocyte, eosinophil and basophil and monocyte counts. The increased leucocyte and neutrophil counts in the second trimester in HbAA and third trimester in HbAS may be due to genetic factor and/or oestrogen secretion reaching production peak at different periods of pregnancy. The relative increase in these haematological indices in HbAS women may be a protective mechanism against infection during pregnancy.     

Cytokine expression in peripheral blood lymphocytes indicates a switch to T(HELPER) cells in patients with preeclampsia

We sought to determine whether cytokine expression in peripheral blood mononuclear cells is altered in patients with preeclampsia and in patients with a history of recurrent spontaneous abortion (RSA). Twenty-four patients with preeclampsia and twenty patients with a history of RSA were included into the study. Two control groups consisted of twenty healthy pregnant and twenty healthy non-pregnant women. The intracellular expression of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined in peripheral blood mononuclear cells (PBMCs) by flow cytometry as a measure of cytokine production. IL-2 synthesis was significantly elevated in the third trimester in preeclamptic patients in comparison with the control group. Non-pregnant women with RSA showed a significantly lower expression of IFN-gamma compared to the non-pregnant control group. Our data suggest an abnormal immune response in preeclamptic patients characterised by a shift to a predominantly Th1-type immunity.     

Effect of IgG therapy on lymphocyte subpopulations in the peripheral blood of Kuwaiti women experiencing recurrent pregnancy loss

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.     

Urinary neopterin levels in the different stages of pregnancy

BACKGROUND/AIMS: Neopterin is a biochemical marker of activated cell-mediated immune response which increases in pathological conditions associated with cellular immune activation as well as in pregnancy where cellular immune response is predominant. The aim of this study was to determine the urinary neopterin level in each trimester of pregnancy and to determine if it can be used as a marker. METHODS: 104 healthy pregnant women (mean age 22.10 +/- 4.39 years; 36 in the first, 30 in the second and 38 in the third trimester) and 16 non-pregnant healthy women (mean age 20.94 +/- 4.48 year) were included. RESULTS: The mean urinary neopterin concentration of all pregnant women was higher than that of non-pregnant women (166.4 +/- 31.7 and 103.1 +/- 27.5 micromol/mol creatinine respectively, p < 0.01). The mean urinary neopterin levels in each trimester and non-pregnant women were 139.8 +/- 49.6, 131 +/- 40.2, 227.9 +/- 86.5 and 103.1 +/- 27.5 micromol/mol creatinine, respectively. Urinary neopterin levels were not significantly different between non-pregnant, first and second trimester groups, but were significantly higher in the third trimester than each of these groups (p < 0.05, p < 0.01 and p < 0.01 respectively). CONCLUSION: Urinary neopterin levels increase significantly in the third trimester probably due to more predominated cellular immunity. The pathologies causing cellular immune activation, especially in the first two trimesters can be predicted with urinary neopterin levels.     

CD26 and CD30 expression on the surface of lymphocyte during normal pregnancy

It is increasingly apparent that the Th1/Th2 cell ratio is decreased during pregnancy. In a previous study, we revealed that combined analysis of soluble CD26 and CD30 might be a potent surrogate tool for evaluating the Th1/Th2 balance during pregnancy. Therefore, in the present study, we elucidated whether the CD26 and CD30 expression on the surface of lymphocyte is useful marker for Th1 and Th2 lymphocytes, respectively, during pregnancy with flow cytometric technique. The peripheral blood samples were obtained from 6 non-pregnant healthy women, 8 healthy pregnant women in the first trimester and 12 pregnant women in the third trimester. The mean percentages of CD26 expression did not differ significantly among these groups (p = 0.45). Also, the mean percentages of CD30 expression did not differ significantly among these groups (p = 0.32). From the present study, the expression of CD26 and CD30 did not appear to be a useful marker for Th1 and Th2 lymphocytes during pregnancy.     

Decreased levels of circulating CD4+ T lymphocytes during normal human pregnancy

Peripheral blood mononuclear cell (PBMC) populations during human pregnancy have been investigated by many authors, although the different results obtained, principally in relation to T cells, are very discrepant. In this study we aimed to exclude all the possible causes of these discrepancies: small sample size; diurnal rhythm of CD4+ T cells; smoking habits; haemodilution which occurs during pregnancy and inappropriate statistical analysis; in order to determine whether gestation has a definite effect on PBMC populations. We found that the percentage of CD4+ T lymphocytes decreases in the first and second trimesters, returns to the non-pregnant level in the third trimester and remains there in the postpartum period. The percentages of CD3+ T lymphocytes run parallel to those of CD4+ while CD8+ T lymphocytes do not vary. The proportion of CD16+ cells, which include mature NK cells, diminishes in the second trimester and this reduction is maintained in the third trimester and the puerperium. No variation was found in the other PBMC studied (CD20+ lymphocytes, CD14+ monocytes and D/DR+ cells). When parity was considered no difference was seen between primiparous and multiparous women in any of the cell populations tested.     

Changes in lymphocyte subsets during pregnancy and post-partum in cases of beginning eclampsia

AIMS: The goal of the present retrospective study was to examine the peripheral blood lymphocytes for expression of phenotypic and activation markers concerning the development of hypertension in pregnancy. METHODS: 16 women (aged 25-43 years; mean 35.1) developing hypertension in the third trimester (week 25-34) have had blood samples taken in the first (< 14 weeks), the second (week 14-23), the third trimester (week 24-35), in late pregnancy (week 36-termination of pregnancy) and within 1 week post-partum, The control group consisted of 16 age-matched pregnant healthy women, who underwent the same regime. All blood samples were taken in the morning, stored at room temperature and stained within 6 hours and measured within 24 hours. Kruskal-Wallis analysis of variance between both groups was done with multiple comparison according to Dunn. RESULTS: Comparing both groups, the total white cell count was significantly increased in all pregnancies and post-partum. In case of hypertension in pregnancy the cell numbers of suppressor/cytotoxic (CD 8+) and CD 56(+)-activated T cells showed a significant increase in the first trimester (< 14 weeks) [p < 0.05] and decreased thereafter to normal values. In the second trimester (week 14-23) helper/inducer lymphocytes and CD 56+/CD 3+ lymphocytes decreased in case of pre-ecclampsia and cytotoxic lymphocytes elevated [p < 0.05]. In the third trimester (week 24-35) there was no difference in both study groups and in late pregnancy (week 36-termination) there were only small differences without statistical significance. Within 1 week postnatal the value of Il-2 receptor T lymphocytes decreased in the group of pre-eclampsia in comparison to normal pregnancies [p < 0.05]. CONCLUSIONS: Regarding the major changes in activated T cells in both study groups no specific pattern of lymphocyte subsets in case of pre-eclampsia could be found in comparison to healthy pregnant women. Further investigations should focus on functional activation and/or suppression of the cellular immune system. Perhaps this could lead to a screening test for pre-eclampsia in future, which is non-invasive for the patient and economic for our social community because it might reduce medical costs.     

Mature adrenomedullin concentrations in plasma during pregnancy

Objective: Adrenomedullin is a novel peptide that exerts a potent, dose-dependent and long-lasting hypotensive effect. In human plasma, adrenomedullin consists of two molecular forms: mature and immature. Immature adrenomedullin is much less bioactive than mature adrenomedullin. Although a gradual increase in plasma adrenomedullin has been reportedly observed as pregnancy progressed, mature adrenomedullin has not been examined. The aim of this study was to elucidate the plasma level of mature adrenomedullin in pregnant women. Methods: We measured the concentrations of mature adrenomedullin in ten pregnant women in the first trimester, ten pregnant women in the third trimester, and ten non-pregnant controls with the immunoradiometric assay. Results: The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the first trimester compared to age-matched non-pregnant subjects (p < 0.05). The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the third trimester compared with pregnant women in the first trimester (p < 0.005). Conclusion: Our study demonstrated that concentrations of mature adrenomedullin were elevated in pregnant women compared with non-pregnant women and its concentration in the third trimester was significantly higher than that in the first trimester.