Normal Non-pregnant Controls Research Articles

The bivariate NRIP1/ZEB2 RNA marker permits non-invasive presymptomatic screening of pre-eclampsia

Using genome-wide transcriptome analysis by RNA sequencing of first trimester plasma RNA, we tested whether the identification of pregnancies at risk of developing pre-eclampsia with or without preterm birth or growth restriction is possible between weeks 9–14, prior to the appearance of clinical symptoms. We implemented a metaheuristic approach in the self-learning SVM algorithm for differential gene expression analysis of normal pregnancies (n = 108), affected pregnancies (n = 34) and non-pregnant controls (n = 19). Presymptomatic candidate markers for affected pregnancies were validated by RT-qPCR in first trimester samples (n = 34) from an independent cohort. PRKG1 was significantly downregulated in a subset of pregnancies with birth weights below the 10thpercentile as shared symptom. The NRIP1/ZEB2 ratio was found to be upregulated in pregnancies with pre-eclampsia or trisomy 21. Complementary quantitative analysis of both the linear and circular forms of NRIP1 permitted discrimination between pre-eclampsia and trisomy 21. Pre-eclamptic pregnancies showed an increase in linear NRIP1 compared to circular NRIP1, while trisomy 21 pregnancies did not.

Reduced frequency and functional defects of CD4+CD25highCD127low/\u2212 regulatory T cells in patients with unexplained recurrent spontaneous abortion

BackgroundUnexplained recurrent spontaneous abortion (URSA) is defined as two or more consecutive pregnancy losses, generally of unknown cause; it is related to a failure of fetal–maternal immunological tolerance. Regulatory T cells (Tregs) exert immunosuppressive effects, which are essential to maintain fetal–maternal immunological tolerance and regulate immune balance. In this study, we used the specific cell-surface phenotype of CD4+CD25highCD127low/− Tregs to investigate the number and suppressive function of Tregs isolated from the peripheral blood of patients with URSA with the aim of expanding our understanding of their role in URSA.MethodsWe isolated a relatively pure population of peripheral CD4+CD25highCD127low/− Tregs and CD4+CD25− responder T cells (Tresps) from the patients with URSA and normal fertile nonpregnant control women via fluorescence-activated cell sorting. We compared the frequency, suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls.ResultsThe frequency of CD4+CD25highCD127low/− Tregs in the peripheral blood was lower in URSA patients than in the controls (P < 0.05). The mean fluorescence intensity of FOXP3 and FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients (P < 0.01). Tregs suppressed the activity of autologous Tresps stimulated with anti-CD3/CD28 beads in a concentration-dependent manner, with the strongest suppression occurring in cocultures with a 1:1 Treg:Tresp ratio in both groups; however, patient-derived Tregs exhibited a poorer capacity to suppress the proliferation of autologous Tresps than the Tregs from normal controls (P < 0.01). Moreover, Tregs isolated from URSA patients inhibited the proliferation of Tresps from normal controls less potently than the Tregs from normal controls (P < 0.01), and Tresps from URSA patients were less effectively suppressed by autologous Tregs than by those from normal controls (P < 0.01). Tresp activity were intact in both groups.ConclusionsWe observed a lower frequency of peripheral CD4+CD25highCD127low/− Tregs with lower FOXP3 expression in the peripheral blood of URSA patients. In addition, highly purified Tregs from patients with URSA exhibited impaired suppressive effects. The defect in immune regulation in URSA patients appears to be primarily related to impaired Tregs, and not to increased resistance of Tresps to suppression. Our findings reveal a potential novel therapeutic target for URSA.

Hematological Changes, Serum Interferon Gamma and Interleukin-4 Alterations in Normal Pregnancy and Preeclampsia

Background: Various hematological and immunological changes can occur in pregnancy which could be beneficial for the growth of the fetus and the maintenance of the pregnancy although some of these changes could be hazardous to the fetus and can cause complications during pregnancy. Thus, this study was conducted to investigate the hematological and immunological changes in normal pregnancy and preeclampsia (PE). Materials and Methods: To this end, hematological and immunological changes were evaluated in 62 normal pregnant women and 56 pregnant women with PE. Moreover, 58 healthy non-pregnant women were studied as the control group. The study was done between December 1, 2018 to May 1, 2019 in Chwarbakh Private Clinic and Shorsh Teaching Hospital. The venous peripheral blood from the antecubital vein was used in this study. Results: The results revealed a significant increase in the number of granulocytes, monocytes, and mean platelet (PLT) volume in both normal pregnant women and PE patients in comparison to normal (non-pregnant) controls (P&lt;0.01). In addition, there was a significant correlation between a reduction in their hematocrit (HCT), PLT, and lymphocytes (P&lt;0.01). With regard to immunological changes, a significant increase was also observed in the serum interleukin-4 (IL-4) levels in both normal pregnancy and preeclamptic patients when compared to non-pregnant controls (P&lt;0.01), but gamma interferon was not significantly different. Conversely, there were no significant associations between the serum level of antiphospholipid antibodies and anticardiolipin antibodies in the study groups except for antiphospholipid antibodies which were significantly lower in the third trimester of pregnancy in the preeclamptic patients (P&lt;0.05). Conclusion: In general, significant changes in hematological and immunological parameters were observed in both normal pregnant and PE patients although further studies are required to include more immunological parameters.

Overactivation of Complement Alternative Pathway in Postpartum Atypical Hemolytic Uremic Syndrome Patients with Renal Involvement.

Postpartum atypical hemolytic uremic syndrome (aHUS) is a life-threatening syndrome with unclear pathogenesis. The current study aimed to investigate the clinical and pathological features, complement activation status, and the genetic variations in a Chinese cohort of patients with renal biopsy-proven postpartum aHUS. Five patients with postpartum aHUS were recruited. Renal biopsy specimens were examined and scored. Plasma levels of complements were detected, and coding sequences of complement regulators were screened. Anti-CFH/CFI autoantibodies were further detected. Patients with postpartum aHUS patients presented with severe clinical manifestations and renal involvement. The renal biopsies of the five patients showed typical features of thrombotic microangiopathies. The levels of the following complement components, C4d, Bb, C3a, C5a, and SC5b-9, were significantly elevated in patients with postpartum aHUS compared with normal non-pregnant controls. The plasma levels of CFH and CFI significantly decreased in patients with postpartum aHUS compared with normal pregnant women. Three CFH single nucleotide polymorphisms (SNPs) were identified in the five patients. Two patients presented with CFH autoantibodies. Postpartum aHUS is a clinical syndrome with severe renal damage. Genetic deficiencies and autoantibodies of CFH may lead to alternative pathway overactivation and participated in the pathogenesis of postpartum aHUS.

Antioxidant Enzymes in Gestational Diabetes: A Study on a Kuwaiti Population

Objectives: We hypothesize that enzymatic antioxidants are significant contributors to antioxidant status in gestational diabetes (GDM) through scavenging of free radicals. Methods: We evaluated total antioxidant activity and the activities of two major physiological antioxidant enzymes: glutathione peroxidase (GPX) and superoxide dismutase (SOD) in peripheral blood of 22 pregnant Kuwaiti women in second trimester afflicted with GDM, 28 healthy pregnant women (also in 2nd trimester) and 27 healthy non-pregnant women. Enzyme activities were measured using spectrophotometric assays. Results: No significant differences were noted in total antioxidant activity in peripheral blood in the three cohorts; however, serum SOD activity was significantly decreased in blood of both GDM women (p<0.05) and healthy pregnant subjects (p<0.05) relative to the non-pregnant cohort. Conversely, the activity of GPX was significantly elevated in blood of GDM-afflicted women relative to non-pregnant (p<0.001); and healthy pregnant women (p<0.001). GPX/SOD ratio was significantly higher in the GDM group compared to normal pregnancy and nonpregnant control (P<0.01). Conclusion: The activity of GPX /SOD ratio may be a marker of glycemic control in women with gestational diabetes. It is reasonable to conclude that the pathogenesis of GDM may involve the release of substantial quantities of mediators. This phenomenon suggest further investigation in the management of GDM which may involve other therapeutic targets for pharmacological intervention.

Serum cytokine levels and T lymphocyte subsets in pregnant women with eclampsia

Background: Eclampsia, defined as the occurrence during pregnancy of hypertension, oedema, proteinuria and/or other neurologic abnormalities, causes substantial morbidity and mortality for both mother and foetus. However, its aetiology is largely unknown. Genetic and immune factors may play a role including a reduced maternal response to paternal antigen and an altered adaptation of the maternal immune system to the foetus. Methods: Participants consisted of pregnant women with and without a diagnosis of eclampsia (N = 20, each group), and normal healthy nonpregnant controls (N = 18). Women with smear positive malaria or clinical infections were excluded. Serum levels of TNFα and IL-10 were assayed by ELISA. T lymphocyte subsets of pregnant patients with and without eclampsia were also studied by direct immunofluorescence using monoclonal antibodies and compared with the control group of 18 normal healthy nonpregnant women (NHC). Results: Eclampsia was associated with significantly lower mean serum IL-10 levels compared to normal pregnant and nonpregnant controls. Levels of the pro-inflammatory cytokine TNFα were higher in pregnant women with and without eclampsia, compared to control nonpregnant women. Further differences on serum cytokine levels were observed in the significantly increasing ratio of IL-10 to TNFα from nonpregnant controls to normal pregnant women and to pregnant women with eclampsia. The mean values of CD3+ and CD4+ positive lymphocytes was significantly decreased in patients with eclampsia (p < 0.05) in this study compared to pregnant controls. Similarly, CD3+ and CD4+ T cells were further decreased in eclampsia and pregnant controls compared to nonpregnant controls (p < 0.05). A decreasing CD4/CD8 ratio was observed from non-pregnant to pregnant controls and to patients with eclampsia buttressing an increase in CD8+ cells in eclampsia and pregnancy compared to controls. Conclusions: While a pro-inflammatory immune milieu during pregnancy complicated with eclampsia was demonstrated, the presence of eclampsia was not associated with further cytokine differences.

Establishment of self-sequential longitudinal reference intervals of maternal thyroid function during pregnancy

The objective of this study is to establish self-sequential longitudinal reference intervals of thyroid function in normal pregnant women. According to the selection criteria, 301 cases were taken as the normal pregnant population to establish a normal reference range. Meanwhile, 150 healthy women were selected as the normal non-pregnant control group. To establish their own self-sequential longitudinal reference intervals, we collected samples five times in every case throughout the gestation (including first trimester, second trimester, third trimester, prenatal and postpartum), and detected the levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibodies (TPO-Ab), and then established the self-sequential longitudinal reference intervals. The levels of TSH, FT4 and TPO-Ab were quantified by electrochemistry immunoassay (ECL) and statistically analyzed using SPSS 13.0 software. Serum TSH of normal pregnant women was at a low level in the first trimester (P < 0.05) and began to rise continuously. Not until prenatal phase was it restored to the non-pregnant state (P > 0.05). During pregnancy, serum FT4 of normal pregnant women were consistently lower than non-pregnant levels (P < 0.05) and kept at low levels. Serum TPO-Ab increased significantly in the third trimester and prenatal phase (P < 0.05). Of normal pregnant women, 6.5% were TPO-Ab positive. In conclusion, the reference intervals in our case will reflect the changes of thyroid function in pregnant women more realistically, resulting in a more accurate value for clinical diagnosis and therapy.

Investigation of Soluble HER2 and Transforming Growth Factor Beta-1 Serum Levels in Gestational Trophoblastic Disease

HER2/neu and TGF-beta1 are over-expressed in various types of malignancies. It appears that they play an important role in the biologic behavior of tumors and have prognostic value. Gestational tropoblastic diseases (GTDs) comprise of a heterogeneous group characterized by abnormally proliferating trophoblastic tissues, ranging from benign to malignant. The objective of this study was to measure and compare the serum levels of s-HER2 and TGF-beta between patients with GTDs and pregnant and non-pregnant controls. Serum levels of s-HER2 and TGF-beta1 were determined by ELISA method in 95 GTD patients (55 complete moles, 32 persistent moles, and 8 choriocarcinoma), 30 normal pregnant controls, and 22 normal non-pregnant controls. Mean serum level of s-HER2 did not differ significantly between patients and controls. TGF-beta1 serum level was significantly higher in GTD patients (20.29 +/- 10.68 pg/ml with 95% confidence interval (CI) of 18.10-22.48 pg/ml) compared with pregnant controls (10.26 +/- 11.84 pg/ml with 95% CI of 5.75-14.76 pg/ml) and non-pregnant controls (7.27 +/- 9.61 pg/ml with 95% CI of 3.01-11.53 pg/ml) (P < 0.001). Our findings suggest that TGF-beta1 serum levels in GTD patients may represent a potential prognostic marker. Further investigations with larger sample size and more frequent sampling are required to elucidate this issue.

The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia

Objectives: Increased free radical activity and lipid peroxidation may be implicated in the pathogenesis of preeclampsia. This study was initiated to assess antioxidant enzyme and trace metals’s status in preeclampsia. Design and methods: The comparision was made between the pregnant women with or without preeclampsia and healthy controls in this study. Samples were obtained from 24 normal nonpregnant (controls), 30 normal pregnant and 21 preeclamptic women in the third trimester. Lipid peroxidation end product, malondialdehyde (MDA), free radical scavenging enzyme activity, superoxide dismutase (SOD) and serum zinc (Zn), copper (Cu) levels were measured in either plasma/serum or erythrocytes of patients. Data were analyzed statistically using Student’s t-test. Results: In the preeclamptic group malondialdehyde, Cu levels were significantly increased, while Zn and SOD levels were significantly decreased compared to normal control group and healthy pregnant women. Conclusions: Our findings give support that radical scavenging SOD is consumed by the increased lipid peroxidation in preeclampsia. This data may indicate an involvement of free radicals in the pathophysiology of preeclampsia. This study suggests a relationship between increased MDA, Cu levels and decreased SOD, Zn levels in pregnancy and preeclampsia.

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures

Objective: To describe the prevalence of annexin V antibodies (aANX) in women with early recurrent pregnancy losses (RPLs) or recurrent IVF-ET failure.Design: Retrospective data analysis.Setting: %Tokai University Hospital, Kanagawa, Japan.Patient(s): Two hundred thirty-eight patients with RPLs, 48 patients with recurrent IVF-ET failure and 179 nonpregnant and 120 pregnant control group women.Intervention(s): None.Main Outcome Measure(s): ELISA was used to measure autoantibodies to annexin V.Result(s): An ELISA system developed for aANX revealed a dose-dependent relationship between annexin V and aANX. The positive/negative cutoff was set at 7 multiples of the median based on the 99th percentile of normal nonpregnant control group patients. Patients with RPLs (5.5%) or recurrent IVF-ET failure (8.3%) had a significantly increased incidence of aANX (IgG) compared with normal nonpregnant (1.1%) or pregnant control group women (0), whereas the prevalence of aANX between both patient groups or between both control groups was not statistically different. Specificity was confirmed by absorption studies using annexin V and by immunoblots.Conclusion(s): Our data show that aANX are associated with both RPLs and IVF-ET failure. We propose that anti-annexin V antibodies should be considered a risk factor for these reproductive failures.

31P magnetic resonance spectroscopy of the liver in HELLP syndrome.

Using magnetic resonance spectroscopy (MRS) to measure phosphorus-containing metabolites in the liver, this study aimed to investigate non-invasively whether or not women with haemolysis, elevated liver enzymes and low platelets (HELLP) have detectable abnormalities of hepatic energetics. John Radcliffe Hospital, Oxford. Prospective study. After giving informed consent, patients with HELLP syndrome (n = 7) and controls with severe pre-eclampsia (n = 3), were studied by 31P MRS of the liver as soon as possible after delivery (range 2-4 days) and compared with normal nonpregnant controls (n = 6). Haematological and biochemical tests were performed serially and on the day of the MRS in all pregnant patients. The severity of HELLP varied as follows: peak aspartate aminotransferase (range 129-2574), peak gamma glutamyl transferase (range 28-96), peak lactate dehydrogenase (range 305-2820), nadir platelets (range 25-114), peak international normalised ratio for prothrombin time (before fresh frozen plasma) (range 0.9-1.9). One pregnancy was terminated but all others resulted in live births and all mothers made uneventful, rapid recoveries. MRS-determined relative hepatic concentrations of phosphorus-containing metabolites and absolute concentrations of adenosine triphosphate did not differ significantly between groups. One patient with the most clinically severe HELLP syndrome (by laboratory criteria) exhibited magnetic resonance spectra which showed a relative increase in phosphomonoester and an absolute decrease in hepatic adenosine triphosphate (to 62% of control). Enthusiasm for the conservative management of HELLP syndrome that develops remote from term has been tempered by the inability to identify patients at risk for progression to hepatic necrosis. We found that most patients with HELLP syndrome had normal liver metabolism as assessed by MRS. However, clinically severe HELLP syndrome can be associated with disturbed hepatic metabolism consistent with that seen in hepatic ischaemia and/or granulocytic infiltration of the liver.

Low in vitro Thyrotropic Activity of a Human Chorionic Gonadotropin Molecule in the First Trimester during Pregnancy

Rat thyroid cell strain FRTL-5 is widely used to analyze thyroid stimulators, and responds to purified hCG with increased cyclic AMP production. The aim of this study was to determine the in vitro thyrotropic activity of an immunological hCG molecule according to gestational age during normal pregnancy using the FRTL-5 cell culture system. Sera were collected from 7 normal nonpregnant control and a total of 72 normal pregnant women. Seventy-two pregnant women consisted of 40 women in the first trimester (7–14 weeks’ gestational age (GW) (group I)), 16 women in the second trimester (15–28 GW, group II), and 16 women in the third trimester (29–40 GW, group III). Concentrations of serum hCG and FT₄ of group I were higher than those of groups II and III (p < 0.001). In the in vitro assay, the supernatants were subjected to radioimmunoassay for cAMP. In order to analyze in vitro thyrotropic activity of an immunological hCG molecule, cAMP accumulation rate expressed as cAMP accumulation (nM) divided by maternal serum concentration of hCG (IU/ml) was determined in all three groups. By regression analyses, a statistically significant positive correlation was observed between serum hCG concentration and cAMP accumulation in group I (r = 0.399; p < 0.05), group II (r = 0.915; p < 0.0001) and group III (r = 0.671; p < 0.01). cAMP accumulation rate in group I (0.355 ± 0.022, mean ± SE) was significantly low when compared with group II (0.508 ± 0.051) (p < 0.01) and group III (0.556 ± 0.063) (p < 0.001). Thus, it was found for the first time that the in vitro thyrotropic activity of an immunological hCG molecule in the first trimester was lower than those of the second and the third trimesters. In terms of the in vitro thyrotropic activity, an immunological hCG molecule in the first trimester differs from that of the later trimesters.

Red Cell Deformability in Gestational Hypertension

Erythrocyte deformability and red cell characteristics (MCV, MCHC, Hct) were studied in 18 patients with gestational hypertension, 24 normotensive primigravidae and 20 nonpregnant nulliparous women. The deformability of red cells was determined by red cell filtration in a filtrometer MF4 after prefiltration through cotton wool. We found a statistically reduced deformability in patients with gestational hypertension compared with normal pregnancy and nonpregnant controls. Our data suggest a strong correlation between red cell filterability and newborn weight (r = 0.59, p < 0.02). The deformability of erythrocyte in gestational hypertension mainly depends on the fluidity of the cell membrane (lipid content). Other factors are the hemoglobin viscosity and the cell membrane surface area/cell volume ratio.

Sera from preeclamptic patients contain factor(s) that stimulate prostacyclin production by human endothelial cells

A relative decrease in endothelial cell prostacyclin production may be pivotal in the genesis of preeclampsia. We determined the effect of sera from preeclamptic women on prostacyclin production by monolayers of normal term human umbilical vein endothelial cells. Endothelial cells were incubated with media containing serum from patients with preeclampsia, non-hypertensive, gestational age-matched pregnant controls, or normal non-pregnant controls ( N = 7, all groups). 6-Keto-prostaglandin F 1α, the stable metabolite of prostacyclin, was measured directly in the culture medium by radioimmunoassay. Treatment with preeclamptic sera, when associated with a statistically significant increase in prostacyclin metabolite production by endothelial cells. Thus, sera from women with preeclampsia stimulate rather than inhibit prostacyclin production by endothelial cells. We speculate that there is a factor in the sera of women with preeclampsia that functions to activate endothelial cells or which may play a role in the homeostatic mechanisms to balance reduced prostacyclin output in preeclampsia.

Leucine kinetics and fuel utilization during a brief fast in human pregnancy

To examine proteolysis, protein and leucine oxidation, and fuel utilization during a brief fast (∼17 hours) in human pregnancy, we determined leucine kinetics, urea nitrogen excretion, and respiratory quotient (RQ) in 11 pregnant subjects during the second half of gestation, and in 11 normal nonpregnant controls. The total rate of appearance (Ra) of leucine was similar in the pregnant and control groups (pregnant 4.99 ± 0.60 v control 5.25 ± 1.60 mmol/h [mean ± SD]). However, leucine Ra per kilogram was significantly lower in pregnant subjects (pregnant 68 ± 7 v control 82 ± 13 μmol/kg/h, P < .01). In addition, urinary urea nitrogen excretion was also significantly less in pregnant subjects (pregnant 3.74 ± 1.09 v control 5.58 ± 1.6 mg/kg/h, P < .01). The RQ measured in the pregnant group was significantly higher than controls (0.82 ± 0.05 v 0.76 ± 0.04, P = .01), resulting in higher calculated carbohydrate oxidation rates during fasting in pregnancy. These data suggest that total rates of proteolysis (reflected by leucine flux) are similar in pregnant and nonpregnant subjects after an overnight fast. When normalized to body weight, proteolysis is lower in pregnant subjects. Urea excretion rates are also lower in pregnancy. These findings support the hypothesis that there is a pregnancy-induced adaptation to conserve maternal protein stores during a brief fast. The higher rate of carbohydrate oxidation during fasting in pregnancy may be a reflection of the fetal-placental unit's use of glucose as its predominant oxidative substrate.

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.

Peripheral K cells in normal human pregnancy: decrease during pregnancy and increase after delivery

Peripheral blood levels of K cells were measured in normal pregnant and postpartum women by a plaque-forming cell technique that detects K cells on the basis of their activity of antibody-dependent cell-mediated cytotoxicity (ADCC). Peripheral K cells decreased throughout normal pregnancy ( n = 46; 7.8 ± 3.4%, P < 0.01; 0.13 ± 0.08 × 10 9/1, P < 0.001) and increased in the post-partum period ( n = 17; 14.2 ± 6.1%, P < 0.05; 0.32 ± 0.20 × 10 9/1, P < 0.01) in comparison with those in normal non-pregnant controls ( n = 29; 10.5 ± 4.2%; 0.20 ± 0.09 × 10 9/1). These findings suggest that a decrease of K cells during pregnancy may contribute in part to maternal acceptance of the fetal allograft and that the post-partum increase of K cells may represent a post-partum increase of cell-mediated cytotoxicity, which may contribute to natural defense against puerperal infection.

Protein S and protein C levels in Chinese women during pregnancy, delivery and the puerperium

The plasma levels of protein S and protein C related antigens were determined in a group of normal pregnant Chinese women and a group of normal non-pregnant controls, using the sandwich technique of enzyme immunoassay with commercial kits. Compared with non-pregnant controls, plasma protein S levels were significantly lower during pregnancy, labour, parturition and the early puerperium. There was no significant difference in protein S levels between pregnancy, labour and puerperium. On the other hand, maternal plasma protein C levels during pregnancy and before delivery were similar to those in controls, but a significant increase was found during the third stage of labour. This increase did not persist into the early puerperium. The observed increase in protein C level immediately after delivery in our study may represent a physiological response to counter the tendency towards venous thrombosis in the parturient women, and may help to explain the almost negligible occurrence of thromboembolism in Chinese obstetric patients.

Further studies on immunological parameters in gestational trophoblastic neoplasia

The total blood lymphocyte counts, T-cell counts, B-cell counts, percentage of T cells bearing Fc receptors for IgG (TG), lymphocyte responses to phytohaemagglutinin and concanavalin A and serum IgA levels were measured in 15 patients with hydatidiform mole, 32 patients with malignant trophoblastic disease, 30 pregnant controls, and 34 normal non-pregnant controls. The mean percentage of TG was similar in all four groups but the mean absolute number of TG in patients with malignant trophoblastic disease was significantly lower than that in normal non-pregnant controls, due to the lower mean lymphocyte count and T-cell count in the former group. An immune profile score based on the T-cell count, B-cell count, lymphocyte response to mitogens, and serum IgA level was useful in predicting the subsequent development of malignant trophoblastic disease in patients with hydatidiform mole but was not helpful in predicting resistance to chemotherapy in malignant trophoblastic disease.

Subpopulations of lymphocytes in maternal peripheral blood during pregnancy

The fetus can be considered an allograft with up to one-half of its MHC antigens being potentially recognized by the mother as foreign. This study compares expression of OKT3, OKT4, OKT8, Kappa, Lambda and Ia antigens on lymphocytes in the peripheral blood of normal non-pregnant women, normal pregnant women, patients who are chronic spontaneous aborters and pregnant insulin-dependent diabetic women. Monoclonal antibodies and cytofluorometric analyses were used for these determinations. There were no significant differences ( P = 0.01) between these groups for T-cell markers. A statistically significant ( P = 0.001) increased ratio of cells bearing surface immunoglobulin to those expressing Ia antigen (K&L/Ia) was observed between normal non-pregnant controls and women with a history of chronic spontaneous abortion. It is concluded that T-lymphocytes in the peripheral blood do not demonstrate a phenotypic abnormality that would account for the non-rejection of the fetal allograft; however, women with chronic spontaneous abortion may have abnormal B-cell differentiation or T-cell activation that mediates chronic spontaneous abortion.