The concentrations of soluble HLA-G protein are elevated during mid-gestation and decreased in pre-eclampsia

Article (PDF Available)inFolia Histochemica et Cytobiologica 50(2):286-91 · July 2012with18 Reads
DOI: 10.5603/FHC.2012.0023 · Source: PubMed
The aim of our study was to investigate the dynamics of the alterations of soluble human leukocyte antigen-G (sHLA-G) concentrations in sera of healthy non-pregnant women, as well as healthy pregnant women and patients with pre-eclampsia. Thirty five patients with pre-eclampsia, 52 healthy pregnant women, and 24 healthy non-pregnant women were included in the study. Sera concentrations of sHLA-G protein were determined using the immunoenzymatic ELISA method. Statistical analysis was performed using ANOVA and Mann-Whitney U tests. The concentrations of sHLA-G protein in sera of pregnant women in the first, as well as the second and third, trimesters of normal pregnancy were significantly higher in comparison with healthy nonpregnant women. The sera concentrations of sHLA-G in pregnant women in the second trimester of pregnancy were significantly higher compared to the first and third trimesters. The concentrations of sHLA-G in sera of patients with pre-eclampsia were significantly lower than in pregnant women in the third trimester of physiological pregnancy. The results of our study suggest that normal physiological pregnancy is associated with elevated sera concentrations of sHLA-G molecule. The increased concentrations of sHLA-G molecule in mid-gestation could suggest a role for the protein in the second phase of a physiological invasion of extravillous cytotrophoblast to spiral arteries. Furthermore, the results could suggest a role for the decreased sera concentrations of sHLA-G in the pathogenesis of pre-eclampsia.

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Available from: Jacek JR Rolinski, Feb 18, 2014
    • "Allelic imbalance is common in humans and has lately been described to be of clinical relevance in cancer (Shen et al., 2011). Nucleotide variation in the non-coding parts of the HLA-G gene seem to influence the expression of HLA-G, and a range of studies have reported abnormal levels of HLA-G in the maternal blood and in the placenta in pre-eclampsia and in spontaneous abortions (Colbern et al., 1994; Hara et al., 1996; Yie et al., 2005; Hackmon et al., 2007; Steinborn et al., 2007; Rizzo et al., 2009; Darmochwal-Kolarz et al., 2012; Zhu et al., 2012). However, no studies have investigated correlations between HLA-G genetics, mRNA expression and the expression levels of membrane-bound HLA-G on trophoblast cells simultaneously. "
    [Show abstract] [Hide abstract] ABSTRACT: The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3′-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications.
    Full-text · Article · Nov 2014
  • [Show abstract] [Hide abstract] ABSTRACT: Abstract Preeclampsia, intrauterine growth retardation (IUGR), oligohydramnios, abortus, preterm birth and preterm rupture of the membranes (PROM) are significant complications of pregnancy. Insufficient trophoblastic invasion plays an important role in the pathophysiology of pregnancy complications. Soluble human leukocyte antigen-gestation (HLA-G)1/G5 is a molecule associated with trophoblast invasion. When pregnancy complications are predicted early, strategies to prevent these complications can be implemented. The aim of this study was to investigate the relationship between first trimester maternal serum soluble HLA-G1/G5 levels and high-risk pregnancies. A total of 232 pregnant women were followed prospectively. Maternal blood samples were collected for determination of soluble HLA-G1/G5 levels at 11-14 weeks, during which routine serum free beta human chorionic gonadotropin (βhCG) and pregnancy associated plasma protein-A (PAPP-A) level determinations in addition to nuchal translucency (NT) measurements for Down's syndrome screening were being made, in addition to 20-22 weeks gestation. The subjects were classified into normal pregnancy, preeclampsia, oligohydramnios, IUGR, preterm birth, and PROM groups. First trimester maternal serum soluble HLA-G1/G5 levels were not significantly different between the groups. First trimester soluble HLA-G1/G5 did not predict high-risk pregnancies. Studies with larger number of cases are need to confirm our findings.
    Article · Jun 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Previous studies showed that aberrant HLA-G expression in trophoblast cells plays important roles in trophoblast invasion; however, the mechanisms remain to be explored. In this study, we found that suppressed HLA-G expression could dramatically decrease the mRNA and protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9, and in the proteome assay, there were 3 identified proteins namely, prefoldin 1, eukaryotic translation elongation factor 2 and malate dehydrogenase 2, which were verified by Western blot and known to be associated with invasion, cell cycle and cell metabolism, respectively. Collectively, our study indicated a potential involvement of HLA-G in autocrine networks that may regulate prefoldin, MMPs and trophoblast invasion at the maternal-fetal interface in human pregnancy.
    Article · Nov 2013
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