Pregnancy-specific Β1-glycoprotein Research Articles

Effect of Short Peptides of Pregnancy-Specific β1-Glycoprotein on Differentiation of Human Regulatory T Cells In Vitro and on Their Cytokine Profile.

Pregnancy-specific β1-glycoprotein (PSG), one of the most important proteins of pregnancy, has a pronounced immunosuppressive effect. Short peptides of PSG, the so-called SLiMs (short linear motifs), are promising molecules for mild immunosuppression. We studied in vitro effect of short PSG peptides (YACS, YQCE, YVCS, and YECE) on differentiation and cytokine profile of human T-regulatory lymphocytes (Treg). T helpers isolated from the peripheral blood and polarized into the Treg phenotype with a T-cell activator (anti-CD2/3/28) and the cytokines IL-2 and transforming grown factor β (TGFβ) were used. PSG peptides were shown to have no direct modulatory effect on Treg differentiation in a culture of CD4+ cells polarized to the Treg phenotype. At the same time, PSG peptides had no effect on the viability and number of CD4+ cells in the in vitro culture. PSG peptides also had no effect on the levels of TNFα, IL-8, IL-2, macrophage inflammatory protein 1β, IL-17, IL-10, IL-6, granulocyte-macrophage CSF, monocyte chemoattractant protein 1, IL-13, IL-5, IL-7, IL-12(p70), IL-1β, granulocyte CSF, IL-4, but decreased IFNγ levels. The observed ability of the YQCE peptide to reduce the production of this proinflammatory Th1 cytokine by T helper cells can be interpreted as a positive effect. Our findings can be used for further development of safe peptide drugs based on SLiMs sequences.

Effect of pregnancy-specific β1-glycoprotein on the expression of arginase-1 and indolamine-2,3-dioxygenase by myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSC) - a population of immature cells of myeloid origin with inhibitory functions, mainly related to T lymphocytes. Normally, MDSC account for less than 1% of leukocytes in peripheral blood. The number of these cells increases during healthy pregnancy. However, MDSC have been shown to play a critical role in the maintenance of tumor growth and in autoimmune diseases.
 Because MDSC are now considered important regulators of immunity, finding ways to manipulate their functions is important for the development of therapies for malignant and autoimmune diseases, as well as for pregnancy pathologies and post-transplant complications. The immunosuppressive mechanisms of these cells are mediated by their expression of the surface molecules CD73, ADAM17, PD -L1, the enzymes arginase 1 (Arg 1), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO), reactive oxygen species, and the production of the anti-inflammatory cytokines IL -10 and TGF-1.
 Pregnancy-specific 1-glycoprotein (PSG) is a pregnancy glycoprotein that has immunomodulatory effects on natural (dendritic cells and macrophages) and adaptive (T cells) immunity cells. At the same time, the effect of PSG on MDSC has not been investigated so far. Since this glycoprotein has promising pharmacological applications, it is necessary to study not only the native variant of PSG but also its recombinant form.
 Since the main function of MDSC is immunosuppression, the aim of our work was to evaluate one of its mechanisms, namely the intracellular expression of amino acid degradation enzymes Arg1 and IDO under the influence of native and recombinant PSG in vitro.
 MDSC differentiation was performed from CD11b+ cells isolated from peripheral blood of healthy volunteers. Cells were cultured for 7 days with stepwise addition of GM-CSF, IL -1, and LPS. Native (n) (1, 10, and 100 g/mL) and recombinant (r) (1 and 10 g/mL) PSG was added to the cultures three days before the end of incubation. The percentage of MDSCs (Lin- HLA-DR -CD11b+CD33+) intracellularly expressing Arg1 and IDO was determined by flow cytometry.
 It was found that nPSG and rPSG did not alter the amount of Arg1-expressing MDSCs at all concentrations examined. However, at a concentration of 10 g/mL, both types of proteins caused a statistically significant increase in the percentage of cells expressing IDO.
 We have already established that nPSG and rPSG affect MDSC differentiation by increasing the proportion of these cells belonging to the monocytic subpopulation. However, now we can say that PSG, in addition, enhances the suppressive function of the studied cells.
 The obtained data are novel and open perspectives for targeting myeloid suppressor cells to improve cellular technologies in science and medicine.

Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.

Influence of PSG peptides on the morphofunctional state of the spleen in allogenous bone marrow cell transplantation

It is known that proteins associated with pregnancy provide immune tolerance during pregnancy. One of them is pregnancy-specific β1-glycoprotein (PSG), which has a pronounced immunomodulatory effect. Tetrapeptide fragments (YECE, YQCE, YVCS, and YACS) have been identified in the primary structure of PSG that have immunopharmacological potential. The aim of the study was to evaluate the effect of short peptide fragments of PSG on the morphological and immunohistochemical state of the spleen and its compartments during allogeneic transplantation of a suspension of red bone marrow cells in an in vivo experiment in Wistar rats. It was found that intraperitoneal injection of bone marrow cells in the dynamics of the experiment (35 days) caused splenic hyperplasia with accumulation of lymphoid cells and macrophages in the functional areas of the organ. Administration of short peptide fragments of PSG against the background of allogeneic bone marrow transplantation promotes activation of cells of the immune system in the spleen toward their proliferation (Ki-67) and differentiation, while reducing the content of macrophages (CD68). Thus, short peptide fragments of PSG stabilize proliferative processes and promote the development of adaptive responses in response to an allogeneic graft.

Effect of Pregnancy Specific β1-Glycoprotein on the Replicative Potential of Naïve T Cells and Immune Memory T Cells.

We studied the effects of pregnancy-specific β1-glycoprotein (PSG) on the replicative potential of naïve T cells (CD45RA+) and immune memory T cells (CD45R0+) in vitro by evaluating the expression of the hTERT gene in combination with the proliferative activity of cells. Human PSG was obtained by the author's patented method of immunopurification using a biospecific sorbent with subsequent removal of immunoglobulin contamination on a HiTrap Protein G HP column. We used monocultures of CD45RA+ and CD45R0+ lymphocytes isolated from peripheral blood mononuclear cells of reproductive-age women. It was found that PSG in physiological concentrations inhibited the expression of the hTERT gene mRNA in naïve T cells and immune memory T cells and simultaneously reduced the number of proliferating T cells estimated by the differential gating method. At the same time, PSG reduced CD71 expression only on naïve T cells without affecting this molecule on immune memory T cells. Thus, PSG decreased the replication potential and suppressed the proliferation of T cells and immune memory T cells, which in the context of pregnancy can contribute to the formation of immune tolerance to the semi-allogeneic embryo.

Immunoregulatory potential of pregnancy-specific β1-glycoprotein

The embryo, being half an antigenically “foreign” organism, should elicit a maternal immune response. During evolution, however, the mechanisms ensuring successful development of pregnancy have been formed. In particular, among factors providing immune tolerance during pregnancy are some proteins associated with pregnancy. The pregnancy-specific β 1-glycoprotein (PSG, PSG1; SP1; PSβG1) is a dominant fetoplacental protein produced by cyto- and syncytiotrophoblast cells, and it exhibits immunosuppressive properties. Our team of authors possesses a patented method for obtaining native human PSG preparation from blood serum of pregnant women, a mixture of PSG1, PSG3, PSG7, PSG9, and their isoforms and precursors. This review presents an analysis of our results for the period from 2015 to 2020. We studied the immunoregu-latory effects of the obtained PSG preparation at concentrations comparable to those observed in pregnancy (1, 10, 100 |ag/mL). The study was performed with peripheral blood cells obtained from non-pregnant women. It was found that PSG significantly increased the percentage of adaptive Tregs in vitro, as well as expression of CTLA-4, GITR, and production of IL-10 by these cells. It has been shown that PSG has a stimulating effect upon indoleamine-2,3-dioxygenase (IDO) activity of peripheral blood monocytes. For Th17 cells, we have demonstrated that PSG can suppress differentiation and proliferation of these cells, along with reduced production of critical proinflammatory cytokines (IL-8, IL-10, IL-17, IFNγ, MCP-1, TNF α). As for the memory T cells, PSG suppressed CD25 expression and IL-2 production by them, along with simultaneous decreased expression of Gfi1, hnRNPLL genes, thus preventing the formation of the “mature” CD45R0 isoform. PSG has been shown to inhibit naive T cells’ conversion to the terminally differentiated effector subpopulation of helper T cells. When analyzing PSG effects upon cytokine profile of immunocompetent cells, it was found that the protein predominantly suppresses the Th1 cytokine production by the studied cell types, and regulates the Th2 cytokine production in divergent manner. The results obtained are consistent with general concept of immunosuppression during pregnancy. Thus, PSG could be one of the factors preventing formation and implementation of immune response to placental antigens.

Влияние трофобластического 1-гликопротеина на репликативный потенциал наивных Т-клеток и Т-клеток иммунной памяти

We studied the effects of pregnancy-specific β1-glycoprotein (PSG) on the replicative potential of naive T cells (CD45RA+) and immune memory T cells (CD45R0+) in vitro by evaluating the expression of the hTERT gene in combination with the proliferative activity of cells. Human PSG was obtained by the author's patented method of immunopurification using a biospecific sorbent with subsequent removal of immunoglobulin contamination on a HiTrap Protein G HP column. We used monocultures of CD45RA+ and CD45R0+ lymphocytes isolated from peripheral blood mononuclear cells of reproductive-age women. It was found that PSG in physiological concentrations inhibited the expression of the hTERT gene mRNA in naive T cells and immune memory T cells and simultaneously reduced the number of proliferating T cells estimated by the differential gating method. At the same time, PSG reduced CD71 expression only on naive T cells without affecting this molecule on immune memory T cells. Thus, PSG decreased the replication potential and suppressed the proliferation of T cells and immune memory T cells, which in the context of pregnancy can contribute to the formation of immune tolerance to the semi-allogeneic embryo.

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor β1(TGF-β1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-β1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-β1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Pregnancy-associated proteins and their role in the regulation of t-immune memory cell differentation

The role of chorionic gonadotropin (CG), alpha-fetoprotein (AFP) and pregnancy-specific β-1-glycoprotein (PSG) in the regulation of the processes determining the differentiation and maturation of naive T-cells into memory T-cells has been studied. It has been established that CG, AFP and PSG have a predominantly suppressing effect on the expression of CD28 and CD25 activation markers by naive T-cells (CD45RA+) and memory T-cells (CD45R0+), virtually without affecting the expression of CD71 proliferation marker. It has been established that the differentiation processes of naive T-cells and memory T-cells, under the influence of CG, AFP and PSG, are carried out with changing the expression of the - U2af1l4, Gfi1 and hTERT genes, which regulate the alternative splicing of the Ptprc gene (encoding CD45 molecule). At the same time, CG, AFP and PSG stimulated autocrine production of IL-2 with both naive and memory T-cells. Thus, for the first time, the modulating effects of the above-mentioned fetoplacental proteins in relation to the differentiation and functional activity of immune memory T-cells are shown.

The effect of pregnancy-specific β1-glycoprotein 1 on the transcription factor FOXP3 expression by immunocompetent cells.

The role of human pregnancy-specific β1-glycoprotein (PSG) in the regulation of expression of the transcription factor FOXP3 was studied. It is found that, under conditions of directed induction of phenotypic changes in CD4+ lymphocytes to regulatory T cells (Treg), PSG at high concentrations (10 and 100 μg/mL) increased FOXP3 expression. The evaluation of the spontaneous expression level of FOXP3 mRNA showed that PSG (1 and 100 μg/mL) stimulated the expression of this factor in mononuclear cells and isolated CD4+ lymphocytes. Thus, PSG stimulates FOXP3 expression in immunocompetent cells.

Effect of pregnancy-specific β1-glycoprotein on indoleamine-2,3-dioxygenase activity in human monocytes.

The role of heterogenic human pregnancy-specific glycoprotein (PSG), obtained by the authors' technology, in the regulation of the indoleamine-2,3-dioxygenase (IDO) activity in female blood monocytes has been studied in vitro. PSG stimulated IDO activity under the conditions of induction of the monocytes by interferon-γ. Upon the induction of cell proliferation by lipopolysaccharides, the stimulating effect was obtained only with 10 μg/mL of PSG. Enhanced IDO activity is probably a factor of peripheral immunological tolerance and antimicrobial protection against intracellular infections in the gestation period.

Pregnancy Specific β-1 Glycoprotein 1 is Expressed in Pancreatic Ductal Adenocarcinoma and its Subcellular Localization Correlates with Overall Survival.

Proteins of the pregnancy specific β-1 glycoprotein (PSG) family are renowned for their elevated expression during pregnancy. Only few reports have investigated their expression in adenocarcinomas. We studied the expression of PSG1 in pancreatic adenocarcinoma (PDAC). In a cohort of 104 patient samples, immunohistochemical analysis determined PSG1 expression in every specimen. PSG1 was found at apical and cytoplasmic localization or solely at cytoplasmic localization, with the latter case being correlated to shortened median survival (25 vs 11 months, logrank p-value < 0.001). At the same time, enzyme linked immunosorbent assay (ELISA) did not detect elevated PSG1 levels in the plasma of PDAC patients as opposed to the plasma of healthy, non-pregnant control individuals. We also probed the impact of PSG1 expression in a murine tumor model system, using subcutaneous injection of Colo-26 cells into immunocompetent BALB/c mice. Here, tumor growth was not affected by the expression of human PSG1. Our study reaffirms interest into the tumor-contextual biology of PSG proteins.

Exhaustive analysis of human endogenous retrovirus expression in cytotrophoblast differentiation into syncytiotrophobloast

Normal human term cytotrophoblast cells prepared by trypsin-DNAse I digestion with and without secondary immunological purification with CD9 antibodies were investigated for the expression of morphological and genetic markers of proliferation and differentiation. After 24 h of culture, the cell preparations demonstrated spontaneous formation of microvilli and formation of small syncytial units as assessed by desmoplakin staining and FITC-dextran microinjection. EGF was required for mature syncytial formation. Compared to log-phase proliferating HeLa cells, uptake of [3H]thymidine incorporation was low and quickly decreased to negligible levels. Expression of the proto-oncogenes c-myc, c-fos, and c-jun and historic 2A decreased rapidly in the first 24 h of culture in both cell preparations, followed by an increase in expression of c-fos and junB over the next 3 days of culture. Proto-oncogene changes were similar in attached and suspension cells. Spontaneous increases in ahCG, pregnancy-specific β1-glycoprotein and 3β-hydroxysteroid dehydrogenase (3βOHSD) occurred within 1 day in both cell preparations. EGF receptor blocking antibodies did not inhibit minor degrees of spontaneous syncytial formation nor inhibit spontaneous expression of αhCG or 3βOHSD mRNA, but did prevent extensive syncytialization induced by EGF. The results demonstrate that term cytotrophoblast cells even in serum-free conditions or suspension culture rapidly commit to a non-proliferative differentiation program in culture which includes limited syncytialization and marked hormone mRNA expression. However, EGF is required for extensive syncytial development.

Immunomodulating effects of human pregnancy-specific β1-glycoprotein

Effects of physiological concentrations of human pregnancy-specific β1-glycoprotein (PSG) on the expression of the markers of natural killer (NK) cells, T cells with natural killer functions (NKT), and Tregulatory cells (Treg), as well as on the indoleamine-2,3-dioxygenase (IDO) activity in monocytes and on lymphocyte apoptosis in vitro were studied. It was shown that high PSG concentrations (100 μg/mL) suppressed the expression of CD16/56 by NK cells, while inhibiting the cytolytic activity of these cells. At the same time, low PSG concentrations (1 and 10 μg/mL) enhanced CD16/56 expression by NKT cells, which was associated with cytokine production. It was found that PSG increased the number of adaptive Treg cells (CD4+FOXP3+ and CD4+CD25brightFOXP3+) with suppressor activity in cell culture. In addition, PSG stimulated the IDO activity in peripheral monocytes, further enhancing the generation of Treg cells. On the whole, PSG had an antiapoptotic effect on lymphocytes. The described effects can determine the contribution of PSG to the development of immunological tolerance in pregnancy.

Role of human pregnancy-specific β1-glycoprotein in the regulation of immunological tolerance-associated factors.

Role of human pregnancy-specific β1-glycoprotein in the regulation of immunological tolerance-associated factors.

Estimating the Risk of a Down's Syndrome Term Pregnancy Using Age and Serum Markers: Comparison of Various Methods

The risk of an individual woman having a pregnancy associated with Down's syndrome is estimated given her age, α-fetoprotein, human chorionic gonadotropin, and pregnancy-specific β1-glycoprotein levels. The classical estimation method is based on discriminant analysis under the assumption of lognormality of the marker values, but logistic regression is also applied for data classification. In the present work, we compare the performance of the two methods using a dataset containing the data of almost 89,000 unaffected and 333 affected pregnancies. Assuming lognormality of the marker values, we also calculate the theoretical detection and false positive rates for both the methods.

Correlation between biological activity and conformational dynamics properties of tetra- and pentapeptides derived from fetoplacental proteins

In this work, using molecular dynamics simulation, we study conformational and dynamic properties of biologically active penta- and tetrapeptides derived from fetoplacental proteins such as alpha-fetoprotein, pregnancy specific β1-glycoprotein, and carcinoembryonic antigen. Existence of correlation between flexibility of peptide backbone and biological activity of the investigated peptides was shown. It was also demonstrated that flexibility of peptide backbone depends not only on its length, but also on the presence of reactive functional groups in amino acid side chains that participate in intramolecular interactions. Peptides that demonstrate similar biological effects in regulation of proliferation of lymphocytes and expression of differentiation antigens on their surface (LDSYQCT, PYECE, YECE, and YVCE) are characterized by rigidity of their peptide backbone. Increased backbone flexibility in peptides PYQCE, YQCE, SYKCE, YQCT, YQCS, YVCS, YACS, and YACE is correlated with decreased biological activity. Conformational mobility of amino acid residues does not depend on physicochemical properties only, but also on intramolecular interactions. So, evolutionary restrictions should exist to maintain such interactions in the environment of functionally important sites.

Placenta-Derived, Cellular Messenger RNA Expression in the Maternal Blood of Preeclamptic Women

To perform gene expression profiling and real-time quantitative reverse-transcription polymerase chain reaction (PCR) analysis to identify biomarkers of preeclampsia in cellular messenger RNA (mRNA) from maternal blood. We performed a microarray analysis with five maternal blood samples from women with preeclampsia and five matched control subjects. Up-regulated gene expression was further analyzed through reverse-transcription PCR analysis with 28 consecutive blood samples from women affected with preeclampsia and 29 controls. Both pregnancy-specific beta1 glycoprotein and trophoblast glycoprotein were selected based on microarray analysis. Reverse-transcription PCR analysis detected significantly increased mRNA concentrations among women in the preeclampsia group. When stratified according to mild or severe preeclampsia, 19.2-fold and 41.8-fold increases in pregnancy-specific beta1 glycoprotein and 8.3-fold and 10.6-fold increases in trophoblast glycoprotein were observed, respectively. Among women with hemolysis, elevated liver enzymes, and low platelet count syndrome, 51.6-fold and 13.1-fold increases in pregnancy-specific beta1 glycoprotein and trophoblast glycoprotein were observed, respectively. In the preeclampsia group, pregnancy-specific beta1 glycoprotein correlated with severity of proteinuria (P<.001) and systolic blood pressure (P=.01). The mRNA expression of pregnancy-specific beta1 glycoprotein and trophoblast glycoprotein is up-regulated in cells circulating within blood from women with preeclampsia, and pregnancy-specific beta1 glycoprotein expression is positively correlated with the clinical severity of preeclampsia. II.

Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

BackgroundAPC (Adenomatous polyposis coli) plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process.MethodsTo elucidate the biological dysregulation underlying adenoma formation we examined global gene expression profiles of adenomas and corresponding normal mucosa from an FAP patient. Differential expression of the most significant gene identified in this study was further validated by mRNA in situ hybridization, reverse transcriptase PCR and Northern blotting in different sets of adenomas, tumours and cancer cell lines.ResultsEighty four genes were differentially expressed between all adenomas and corresponding normal mucosa, while only seven genes showed differential expression within the adenomas. The first group included pregnancy specific β-1 glycoprotein 9 (PSG9) (p < 0.006). PSG9 is a member of the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78% (14/18) of FAP adenomas and 75% (45/60) of sporadic colorectal cancer cases tested.ConclusionDetection of PSG9 expression in adenomas, and at higher levels in FAP cases, indicates that germline APC mutations and defects in Wnt signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant adult except in association with cancer, and it appears to be an early molecular event associated with colorectal cancer monitoring of its expression may be useful as a biomarker for the early detection of this disease.

First trimester serum concentrations of placental proteins in singleton and multiple IVF pregnancies: implications for Down syndrome screening

First trimester biochemical trisomy screening is based on serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotrophin (hCG). Our aim was to confirm previously suggested modifications in serum marker concentrations after in vitro fertilisation (IVF) and embryo transfer (ET), and to assess the need of establishing normal medians for trisomy screening in these. We compared 56 singleton pregnancies obtained after ET (of which 40 in gonadotrophin stimulation cycles) with 120 gestation-matched spontaneous controls. For multiple pregnancies, 17 treated cycles were compared with 25 controls. The levels of PAPP-A, hCG, and pregnancy-specific β1-glycoprotein were determined and compared between treated and spontaneous pregnancies. Serum PAPP-A levels were reduced in pregnancies achieved after gonadotrophin-stimulated IVF and ET, and this was more pronounced in earlier gestational stages. SP1 followed the same trend, while hCG tended to be increased, and this not only in pregnancies obtained from gonadotrophin-stimulated but also from oestrogen supported cycles, and with a more pronounced effect in the later gestational ages examined here. Decreased PAPP-A together with increased hCG concentrations produce falsely elevated results in first trimester Down syndrome screening, but we do not recommend the establishment of normal medians for IVF pregnancies due to the variations in stimulation protocols.