Maternal Serum Cytokine Concentrations in Healthy Pregnancy and Preeclampsia

The maternal immune response is essential for successful pregnancy, promoting immune tolerance to the fetus while maintaining innate and adaptive immunity. Uncontrolled, increased proinflammatory responses are a contributing factor to the pathogenesis of preeclampsia. The Th1/Th2 cytokine shift theory, characterised by bias production of Th2 anti-inflammatory cytokine midgestation, was frequently used to reflect the maternal immune response in pregnancy. This theory is simplistic as it is based on limited information and does not consider the role of other T cell subsets, Th17 and Tregs. A range of maternal peripheral cytokines have been measured in pregnancy cohorts, albeit the changes in individual cytokine concentrations across gestation is not well summarised. Using available data, this review was aimed at summarising changes in individual maternal serum cytokine concentrations throughout healthy pregnancy and evaluating their association with preeclampsia. We report that TNF-α increases as pregnancy progresses, IL-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation. Lower second trimester IL-10 concentrations may be an early predictor for developing preeclampsia. Proinflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-8, and IL-6) are significantly elevated in preeclampsia. More research is required to determine the usefulness of using cytokines, particularly IL-10, as early biomarkers of pregnancy health.

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PERBEDAAN RERATA KADAR AKTIVIN A SERUM MATERNAL ANTARA PREEKLAMSIA BERAT DENGAN BUKAN PREEKLAMSIA BERAT

JOURNAL OBGIN EMAS ◽

10.25077/aoj.1.1.30-37.2017 ◽

2019 ◽

Vol 1 (1) ◽

pp. 30-37

Author(s):

Dovy Djanas ◽

Bayu Pramudyo Ariwibowo ◽

Hafni Bachtiar

Keyword(s):

Serum Levels ◽

Activin A ◽

Maternal Serum ◽

Severe Preeclampsia ◽

Inclusion Criteria ◽

Exclusion Criteria ◽

Cross Sectional ◽

Tnf Α ◽

The Mean ◽

In Pregnancy

At the start of preelampsia there is a failure of cytotrophoblst invasion into the maternal spiral arteries that will lead to decreased uteroplacetal perfusion which will be followed by the failure of the unit fetoplacenter to get enough oxygen from the room intervillous that ultimately lead to a state of hypoxia in placenta. This will cause the expenditure of TNF-α dan IL-1β from placenta and a factors called hypoxia-inducible transcription factors that will spur the trophoblast to produce activin A lot more. This research was conducted by cross sectional method in maternal room of obstetrics and gynecology department of Central General Hospital of Dr. M. Djamil Padang from August 2015 until February 2016 with 20 patients of severe preeclampsia and 20 patients not severe preeclampsia, who met inclusion criteria and there is no exclusion criteria. Then performed statistical analysis using Mann-Whitney test to determine difference in mean maternal activin A serum levels of severe preeclampsia and not severe preeclampsia. The mean maternal serum levels of activin A in severe preeclampsia is 32,55 ± 1,84 ng/ml and in pregnancy with no severe preeclampsia is 8,59 ± 0,59 ng/ ml. Difference in mean maternal serum level of activin A in the two groups was statistically significant (p=0,001). Ma-ternal serum activin A levels is significantly higher in severe preeclampsia than pregnancy with no severe preeclampsia.Keywords: Activin A, severe preeclampsia, not severe preeclampsia

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GDF15 Concentrations in Maternal Serum Associated with Vomiting in Pregnancy: the Cambridge Baby Growth Study

10.1101/221267 ◽

2017 ◽

Cited By ~ 3

Author(s):

Clive J. Petry ◽

Ken K. Ong ◽

Keith A. Burling ◽

Peter Barker ◽

John R.B. Perry ◽

...

Keyword(s):

Pregnant Women ◽

Stromal Cells ◽

Geometric Mean ◽

Therapeutic Benefit ◽

Maternal Serum ◽

Second Trimester ◽

Growth Study ◽

The Relationship ◽

Maternal Bmi ◽

In Pregnancy

AbstractNausea and vomiting in pregnancy (NVP) affects 70-90% of all pregnant women but its pathogenesis is unknown. Growth and Differentiation Factor 15 (GDF15), secreted from the trophoblast and decidual stromal cells, is present at high levels in the blood of pregnant women. The receptor for GDF15 has recently been identified and is specifically expressed in the hindbrain where it transmits aversive signals including nausea and conditioned taste aversion. We explored the relationship between GDF15 concentrations in maternal serum during pregnancy and self-reported NVP. In a study of 791 women from the Cambridge Baby Growth Study maternal GDF15 concentrations were higher in women who reported vomiting in the 2nd trimester (geometric mean: 11,670 pg/mL; 95% confidence interval: 11,056-12,318) and were even higher in the eleven women who reported taking anti-emetics during pregnancy (13,376 (10,821-16,535) compared to those who reported no nausea or vomiting during pregnancy (10,657 (10,121-11,222); P=0.02 and P=0.04, respectively, adjusted for gestational age at sampling and maternal BMI). In conclusion serum GDF15 concentrations early in the second trimester of pregnancy are significantly and positively associated with second trimester vomiting and with maternal anti-emetic use. In the context of the recently revealed biology of GDF15 this data suggests that antagonism of GDF15 may have some potential for therapeutic benefit in NVP.

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Inflammatory cytokines in newborn infants

Mediators of Inflammation ◽

10.1080/09629359890811 ◽

1998 ◽

Vol 7 (5) ◽

pp. 309-312 ◽

Cited By ~ 21

Author(s):

A. Sarandakou ◽

G. Giannaki ◽

A. Malamitsi-Puchner ◽

D. Rizos ◽

E. Hourdaki ◽

...

Keyword(s):

Immune Response ◽

Umbilical Cord ◽

Inflammatory Cytokines ◽

Environmental Changes ◽

Mode Of Delivery ◽

Newborn Infants ◽

Serum Levels ◽

Perinatal Period ◽

Maternal Serum ◽

Tnf Α

Serum levels of IL-1β, IL-6 and TNF-α were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls(p<0.0001). IL-1β and IL-6 declined significantly from N1 to N40(p<0.0001), while TNF-α increased significantly from N1 to N5 and declined thereafter. MS∞IL-1β and IL-6, but not MS∞TNF-α, were significantly higher than those of controls(p<0.0001). IL-1β values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1 β, IL-6 and TNF-α during the perinatal period might suggest their involvement in an inflammation like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

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Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

International Journal of Molecular Sciences ◽

10.3390/ijms22147331 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7331

Author(s):

Justyna Szczykutowicz ◽

Joanna Tkaczuk-Włach ◽

Mirosława Ferens-Sieczkowska

Keyword(s):

Immune Response ◽

Seminal Plasma ◽

Immune Modulation ◽

Lectin Affinity Chromatography ◽

Human Seminal Plasma ◽

Plant Lectins ◽

Healthy Pregnancy ◽

Endogenous Lectins ◽

Maternal Immune Response ◽

Inducible Protein

In light of recent research, there is increasing evidence showing that extracellular semen components have a significant impact on the immune reaction of the female partner, leading to the tolerogenic response enabling the embryo development and implantation as well as further progress of healthy pregnancy. Seminal plasma glycoproteins are rich in the unique immunomodulatory glycoepitopes that may serve as ligands for endogenous lectins that decorate the surface of immune cells. Such interaction may be involved in modulation of the maternal immune response. Among immunomodulatory glycans, Lewis type antigens have been of interest for at least two decades, while the importance of T/Tn antigens and related structures is still far from understanding. In the current work, we applied two plant lectins capable of distinguishing glycoepitopes with terminal GalNAc and Gal to identify glycoproteins that are their efficient carriers. By means of lectin blotting and lectin affinity chromatography followed by LC-MS, we identified lactotransferrin, prolactin inducible protein as well as fibronectin and semenogelins 1 and 2 as lectin-reactive. Net-O-glycosylation analysis results indicated that the latter three may actually carry T and/or Tn antigens, while in the case of prolactin inducible protein and lactotransferrin LacdiNAc and lactosamine glycoepitopes were more probable. STRING bioinformatics analysis linked the identified glycoproteins in the close network, indicating their involvement in immune (partially innate) processes. Overall, our research revealed potential seminal plasma ligands for endogenous Gal/GalNAc specific lectins with a possible role in modulation of maternal immune response during fertilization.

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Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy

Microorganisms ◽

10.3390/microorganisms9081749 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1749

Author(s):

Giuseppe Gerna ◽

Chiara Fornara ◽

Milena Furione ◽

Daniele Lilleri

Keyword(s):

Immune Response ◽

Human Cytomegalovirus ◽

Primary Infection ◽

Cytomegalovirus Infection ◽

Hcmv Infection ◽

Antiviral Treatment ◽

Virus Transmission ◽

Immune Correlates ◽

Maternal Immune Response ◽

In Pregnancy

Congenital cytomegalovirus infection (cCMV) may affect about 1% of all newborns all over the world as a result of either a primary or recurrent human cytomegalovirus (HCMV) infection. While about 90% of infants affected by cCMV are asymptomatic at birth, the remaining 10% are symptomatic often with neurodevelopmental impairment and sensorineural hearing loss. In view of identifying the best approach to vaccine prevention of cCMV, this review will examine the most important steps made in the study of the immune response to, and diagnosis of, HCMV infection. The maternal immune response and immune correlates of protection are being partially identified with a partial contribution given by our laboratory. The diagnosis of primary infection is often difficult to achieve in the first three months of pregnancy, which is the time primarily involved in virus transmission to the fetus in association with the most severe symptoms and sequelae. Prevention of cCMV is anticipated by prevention of primary infection in early pregnancy by means of different measures, such as (i) behavioral-educational measures, (ii) immunoglobulin administration, (iii) antiviral treatment with valaciclovir. However, the most promising approach to cCMV prevention appears to be the development of a non-living vaccine, including at least three viral antigens: gB, pentamer complex gHgLpUL128L, and pp65, which have been shown to be able to stimulate both the humoral and the cellular arms of the maternal immune response. Primary HCMV infection may be managed in pregnancy by counseling of the couples involved by a team of specialists that includes virologists, obstetricians, infectivologists and neonatologists.

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Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection

10.1101/2021.11.20.469369 ◽

2021 ◽

Author(s):

Lillian J Juttukonda ◽

Elisha M Wachman ◽

Jeffery Boateng ◽

Mayuri Jain ◽

Yoel Benarroch ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Nk Cells ◽

Control Group ◽

Decidua Basalis ◽

Tnf Α ◽

Show Evidence ◽

Negative Controls ◽

In Pregnancy

While COVID-19 infection during pregnancy is common, fetal transmission is rare, suggesting that intrauterine mechanisms form an effective blockade against SARS-CoV-2. Key among these is the decidual immune environment of the placenta. We hypothesized that decidual leukocytes are altered by maternal SARS-CoV-2 infection in pregnancy and that this decidual immune resonse is shaped by the timing of infection during gestation. To address this hypothesis, we collected decidua basalis tissues at delivery from women with symptomatic COVID-19 during second (2nd Tri COVID, n=8) or third trimester (3rd Tri COVID, n=8) and SARS-CoV-2-negative controls (Control, n=8). Decidual natural killer (NK) cells, macrophages and T cells were evaluated using quantitative microscopy, and pro- and anti-inflammatory cytokine mRNA expression was evaluated using quantitative reverse transcriptase PCR (qRT-PCR). When compared with the Control group, decidual tissues from 3rd Tri COVID exhibited significantly increased macrophages, NK cells and T cells, whereas 2nd Tri COVID only had significantly increased T cells. In evaluating decidual cytokine expression, we noted that IL-6, IL-8, IL-10 and TNF-α were significantly correlated with macrophage cell abundance. However, in 2nd Tri COVID tissues, there was significant downregulation of IL-6, IL-8, IL-10, and TNF-α. Taken together, these results suggest innate and adaptive immune responses are present at the maternal-fetal interface in maternal SARS-CoV-2 infections late in pregnancy, and that infections earlier in pregnancy show evidence of a resolving immune response. Further studies are warranted to characterize the full scope of intrauterine immune responses in pregnancies affected by maternal COVID-19.

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False-Positive Maternal Serum Screens in the Second Trimester as Markers of Placentally Mediated Complications Later in Pregnancy: A Systematic Review and Meta-Analysis

Disease Markers ◽

10.1155/2021/5566234 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Christy L. Pylypjuk ◽

Joel Monarrez-Espino

Keyword(s):

Down Syndrome ◽

Preterm Birth ◽

Pregnancy Complications ◽

False Positive ◽

Meta Analysis ◽

Grey Literature ◽

Maternal Serum ◽

Growth Restriction ◽

Second Trimester ◽

In Pregnancy

Background. Multiple-marker, maternal serum screening (MSS) has been the cornerstone of prenatal diagnosis since the 1980s. While combinations of these markers are used to predict fetal risk of Down syndrome and other genetic conditions, there is some evidence that individual markers may also predict nongenetic pregnancy complications, particularly those related to placental dysfunction. The objective of this meta-analysis was to investigate the utility of false-positive, second-trimester MSS for Down syndrome as a marker of placentally mediated complications amongst singleton pregnancies globally. Methods. Electronic searches of PubMed, Medline, Embase, CINAHL, Web of Science, Scopus, and grey literature to 2019 were performed to identify observational studies comparing risk of pregnancy complications amongst pregnancies with false-positive MSS versus controls. A random-effects model of pooled odds ratios by outcome of interest (stillbirth, preeclampsia, fetal growth restriction, and preterm birth) and subgrouped by type of MSS test (double-, triple-, and quadruple-marker MSS) was used. Results. 16 studies enrolling 68515 pregnancies were included. There were increased odds of preeclampsia (OR 1.28, 95% CI 1.09-1.51) and stillbirth (OR 2.46, 95% CI 1.94-3.12) amongst pregnancies with false-positive MSS. There was no significant association with preterm birth or growth restriction. Conclusions. There is some evidence of an association between false-positive, second-trimester MSS for Down syndrome and increased odds of preeclampsia and stillbirth. Future large-scale prospective studies are still needed to best determine the predictive value of false-positive MSS as a marker of placentally mediated complications later in pregnancy and evaluate potential clinical interventions to reduce these risks.

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Donor T Cell Content Of Whole Bone Marrow Is Responsible For Maternal Immunization Following In Utero Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v122.21.5423.5423 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5423-5423

Author(s):

Erik G. Pearson ◽

Jesse Vrecenak ◽

William Peranteau ◽

Alan W. Flake

Keyword(s):

Bone Marrow ◽

Immune Response ◽

T Cells ◽

T Cell ◽

Hematopoietic Cell Transplantation ◽

Fetal Liver ◽

Maternal Serum ◽

Cell Content ◽

Maternal Immunization ◽

Maternal Immune Response

Abstract Introduction In Utero Hematopoietic Cell Transplantation (IUHCT) represents a potential therapeutic approach for many genetic disorders by inducing mixed hematopoietic chimerism and associated donor specific tolerance. We have shown previously that IUHCT of adult bone marrow (BM) cells in the allogeneic murine model induces a maternal alloimmune response against donor antigen. This results in the transfer of maternal alloantibodies via breast milk triggering an adaptive immune response in the pup with loss of chimerism in 70% of recipients. In contrast to our results, other investigators using a murine model of IUHCT with fetal liver (FL) derived cells, identified no significant maternal alloresponse and implicated prenatal maternal-fetal cellular trafficking and maternal T-cells as a primary mechanism of engraftment loss. As these two different observations have profound implications for clinical IUHCT, we sought to reconcile the data by investigation of differences between the two models. One major difference is the difference in antigen presenting cell (APC) and T cell content between the BM and FL grafts. We hypothesized that depletion of the APC or T-cell content of the donor graft would reduce maternal immunization after IUHCT. Methods Donor APC, defined as macrophages (CD11b+), dendritic cells (CD11c+) and B cells (CD45R/B220+) make up a substantial portion of murine BM and contribute to the allohumoral response by indirect presentation of antigen via class II MHC. Donor T cells (CD3+) have also been implicated in the host immune response by indirect and direct activation of host immune cells. In this series of experiments, Balb/c mice underwent IUHCT at E14 with the following B6 donor cell populations: 1) BM; 2) FL; 3) APC depleted BM (containing an increased relative fraction of T cells) 4) T cell depleted BM 5) APC and T cell depleted BM with T cell add back to 2.5% (to approximate T cell concentration in WBM) 6) CD4 Depleted BM and 7) CD8 Depleted BM. Serial post-natal maternal alloantibody assays measured by Fluorescent Activated Cell Sorting (FACS) analysis were used to quantify the postnatal maternal immune response. Results We found a significant difference in the postnatal maternal humoral response in each of these groups. In the WBM and APC depleted BM groups there was a significant increase in maternal serum IgG levels reaching a 24 fold increase compared to negative controls (no serum) at 4 weeks. When we measured the maternal immune response following IUHCT in the fetal liver and T cell depleted BM groups, both of which have decreased relative CD3+ cells, we found a minimal increase (2 fold) in maternal serum IgG levels at 4 weeks. We could not identify a difference between CD4 depleted and CD8 depleted WBM. Conclusion These findings identify that donor T cells within whole bone marrow are responsible for maternal immunization following IUHCT. Modification of donor cell content may allow IUHCT from non-maternal donor sources by avoiding the maternal immune response. Disclosures: No relevant conflicts of interest to declare.

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Evaluation of the variations and potential clinical use of second trimester serum markers for the detection of pre-eclampsia

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20182904 ◽

2018 ◽

Vol 7 (7) ◽

pp. 2904

Author(s):

Savita S. Gautam ◽

Manmeet Kaur ◽

Naimaa K. Chaudhary ◽

Asha Sharma

Keyword(s):

Adverse Pregnancy Outcome ◽

Serum Marker ◽

Serum Markers ◽

Maternal Serum ◽

Clinical Use ◽

Second Trimester ◽

Chi Square ◽

Adverse Pregnancy ◽

Β Hcg ◽

In Pregnancy

Background: In many areas of world, hypertensive disease in pregnancy is the single most common cause of maternal death. Pregnancy associated hypertension remains unsolved despite decades of intensive research and remains the most significant problem in obstetrics. The aim of present study is to evaluate the variations and potential clinical use of second trimester serum markers for the detection of pre-eclampsia.Methods: In an observational study, estimations of serum of human chorionic gonadotropin (β-hCG) were done in 347 randomly selected women at 13-20 weeks of gestation in august 2015 to may 2016. Multiple of median (MOM) was calculated from charts of norms available for that weeks of pregnancy. The subjects were followed up till delivery for the development of hypertension in pregnancy and results analysed statistically with Chi-square test.Results: Out of 347, 47 women developed hypertyension and 2MOM of β hCG was significantly (P<0.001) elevated in those who developed hypertension compared to normotensive women. In our study group a significant associations between elevations in second trimester β-hCG and development of hypertension was observed. Thus with second trimester serum marker study, prediction of pre- eclampsia is possible at incipient stage and adverse pregnancy outcome can be minimized.Conclusions: Maternal serum β-hCG level was found to be significantly higher in hypertensive group than normal group.

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