Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies

Emmer, P.M.; Steegers, Eric A.P.; Kerstens, Harold M.J.; Bulten, Johan; Nelen, W.L.D.M.; Boer, Kees; Joosten, Irma

doi:10.1093/humrep/17.4.1072

Cited by 71 publications

(42 citation statements)

References 34 publications

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“…This result is consistent with one study which also found no difference in the expression of HLA-G between women with RM and with normal pregnancies (Patel et al 2003), but is contrary to the findings of Emmer et al (2002) who observed a lower intensity of HLA-G staining of decidual EVTs from women with RM compared with those from women with normal pregnancies. However, Emmer et al (2002) examined samples from only two normal pregnancies and nine women with RM; such a sample size is likely to be inadequate to allow valid conclusions to be drawn. Thus, results from this study suggest that RM is not caused by a lack of HLA-G expression by EVTs.…”

Section: Discussionsupporting

confidence: 90%

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Bhalla¹,

Stone²,

Liddell³

et al. 2006

Reproduction

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Recurrent miscarriage affects 1% of all couples attempting pregnancy. Immunological factors are postulated to play a role in the aetiology of recurrent miscarriage because the fetus and placenta are immunologically different from the mother. In particular, altered expression of the, non-classical, class I histocompatibility leukocyte antigen (HLA) molecules has been postulated to play a role in the aetiology of recurrent miscarriage as the fetus and placenta are semi-allogenic to the mother. This study was conducted to examine whether altered expression of the non-classical class I HLA molecules, HLA-G and HLA-E, by cells at the maternofetal interface could play a role in the aetiology of recurrent miscarriage. First-trimester placental and decidual biopsies were obtained from 45 women with recurrent miscarriage and 17 gestation-matched normal controls. These biopsies were screened by immunohistochemistry for HLA-G and HLA-E and isotype-matched control antibodies. Staining was analysed by light microscopy and digital image analysis. In both recurrent miscarriage and normal pregnancy, HLA-G was localised to the extravillous trophoblast. There was no difference in the pattern of HLA-G expression between women with recurrent miscarriage and those with normal pregnancies. HLA-E was localised to the syncytiotrophoblast, villous mesenchymal cells, extravillous trophoblast and several decidual cell types, but staining for HLA-E appeared to be confined primarily to the cytoplasm. There was no difference in the pattern of HLA-E expression between women with recurrent miscarriage and those with normal pregnancies.

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Section: Discussionsupporting

confidence: 90%

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Bhalla¹,

Stone²,

Liddell³

et al. 2006

Reproduction

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“…Although no cause is found in the majority of cases, it has been associated with the antiphospholipid syndromes (1), immunological "intolerance" from altered function of endometrial natural killer (NK) cells (2), the polycystic ovary syndrome (3) and insulin resistance (4). A common mechanism for fetal wastage in RPL is defective implantation.…”

Section: Introductionmentioning

confidence: 99%

“…A common mechanism for fetal wastage in RPL is defective implantation. (2) Even when pregnancy following RPL is ultimately successful, placental function may still be compromised, with higher rates of adverse pregnancy outcomes being reported. (5) Abnormal placentation may be associated with high resistance index (RI) in the uterine artery (UA) Doppler waveform, a finding noted to have high predictive value for conditions associated with placental dysfunction such as preeclampsia, fetal growth restriction and placental abruption.…”

Section: Introductionmentioning

confidence: 99%

Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester

Anumba

Gelany

Elliott

et al. 2009

European Journal of Obstetrics & Gynecology and Reproductiv

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CondensationSerum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester. 3 ABSTRACTObjectives: Defective implantation is a mechanism for recurrent pregnancy loss (RPL). We sought to determine whether the serum expression of human relaxin 2 (RLX) is impaired in women with a history of RPL.Study Design: Employing a prospective case-controlled design we studied 20 pregnant women with a history of RPL and 20 age-matched women with no history of RPL (NRPL). We measured serum relaxin 2 levels by ELISA at 6-8, 10-12, 20, 34 wks gestation and in cord blood, and maternal uterine artery Doppler resistance index (RI) at ≥ 10 wks gestation.Results: Relaxin rose to a peak at 12 wks, and gradually declined towards term. At all gestations, women with a history of RPL had lower RLX levels than women without. At 10-12 wks uterine artery, uterine artery RI correlated with serum RLX for both RPL and NRPL and the presence of a notched waveform in the NRPL group was associated with higher RLX levels than the absence of a notch (mean 2.1 vs.1.3ng/ml, P < 0.05 respectively), and also at 20 wks (2.1 vs. 0.95 ng/ml, P < 0.05 respectively), but did not differ in the RPL group. Umbilical venous RLX was 4-fold higher in the RPL group than the NRPL group. Conclusion.Women with a history of RPL demonstrate attenuated levels of serum RLX across all pregnancy trimesters. How dysregulated RLX metabolism may contribute to adverse pregnancy outcome in RPL requires further investigation.

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“…These proteins, also expressed on the surface of extravillous trophoblasts, are involved in inhibition of cytolytic function of uterine natural killer (NK) cells and protect fetal trophoblasts against maternal NK-cell mediated lysis. Two families of inhibitory NK receptors in humans, killer immunoglobulin-like receptors (KIR -belonging to two or three immunoglobulin [Ig] domains) and receptors known as ILT (immunoglobulin-like transcript), confer protection from NK lysis following interaction with HLA-G (Figure 2) (Emmer et al, 2002). Besides modulating the activity of NK cells, the interaction of HLA-G molecules with inhibitory receptors induces apoptosis among activated CD8 + T-cells and induces an expansion of regulatory T (T reg )-cell populations (Rizzo et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…This points to the potential that the interaction between HLA-G and immunocompetent cells at the placental interface could be critical in determining the outcome of pregnancy. In this regard, it may be critical to look for deviations in these interactions in cases of early pregnancy disorders of unknown etiology (Emmer et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

Arjmand¹,

Samadi

2015

Journal of Immunotoxicology

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HLA-G is supposed to play a pivotal role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. A 14-bp insertion and/or deletion polymorphism in exon-8 has a possible role in HLA-G expression. The present study analyzed the 14-bp insertion/deletion polymorphism in normal pregnancy and recurrent miscarriage patients in order to discover a possible correlation between the 14-bp polymorphism and recurrent miscarriage (RM). In this study, genomic DNA from 200 RM patients and 200 normal fertile control individuals using the routine salting out method were isolated. Exon-8 of HLA-G gene of the two groups were amplified using polymerase chain reaction and analyzed by electrophoresis on 10% non-denaturing polyacrylamide gel electrophoresis containing ethidium bromide and visualized under ultraviolet light. HLA-G allele frequencies and genotypes in RM women and the fertile control group were compared using a Chi-square test. The results showed that there was a difference in allelic frequencies of 14-bp insertion polymorphism between fertile controls and RM patients; the frequency of +14 bp/À14 bp heterozygotes was significantly higher in RM patients as compared with fertile controls. Furthermore, the frequency of +14-bp insertion allele was significantly higher in those with RM as compared with normal fertile controls. From the findings here, it was concluded that a 14-bp insertion/deletion polymorphism in exon 8 could play a possible role in recurrent miscarriages. These results might ultimately be of significance for clinicians and those involved in understanding infertility and RM.

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Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies

Abstract: In pathological pregnancies we show an in-situ altered phenotype of trophoblast and NK cells.

Cited by 71 publications

References 34 publications

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

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