HLA-G1 protein expression is not essential for fetal survival

Ober, Carole; Aldrich, Carrie; Rosinsky, Barbara J.; Robertson, Andrea; Walker, Matthew; Willadsen, Stephanie Ann; Verp, Marion S.; Geraghty, Daniel E.; Hunt, Joan S.

doi:10.1016/s0143-4004(98)90000-5

Cited by 172 publications

(111 citation statements)

References 18 publications

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“…Thus, results from this study suggest that RM is not caused by a lack of HLA-G expression by EVTs. This finding is supported by a previous report of a woman who was homozygous for the HLA-G null allele (Ober et al 1998), who had survived life in utero, as a fetus whose placenta could not express HLA-G, for 9 months. While this study suggests that RM is not associated with a lack of expression of HLA-G protein by EVTs, it remains possible that the HLA-G protein expressed by EVTs in women with RM may be functionally defective.…”

Section: Discussionsupporting

confidence: 86%

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: 86%

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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show abstract

“…Previous description of adult individuals homozygous for mutations that prevent expression of HLA-G1 raised concern on the role of this MHC molecule in promoting maternal-fetal tolerance [42,43]. It was subsequently proposed that other HLA-G isoforms produced by alternative splicing of the mutant allele could be recognized by KIR2DL4 and inhibit maternal NK cells [44].…”

Section: Discussionmentioning

confidence: 99%

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

et al. 2003

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A central issue of reproductive immunology in mammals is why a semi-allogeneic embryo is not rejected by the pregnant mother. This is particularly intriguing since, in different species, the early pregnant uterus is infiltrated by numerous maternal lymphocytes, predominantly NK cells. The human NK cell receptor KIR2DL4 has been implicated in the maternal tolerance to the embryo due to its recognition of HLA-G, a non-classical MHC molecule expressed preferentially in the placenta. Killer cell Ig-like receptors (KIR) are believed to participate in the natural immunity to infection and tumors, but KIR2DL4 has unique structural, functional and genetic features that could confer it a different role. However, we demonstrate here that the KIR2DL4:HLA-G interaction is not essential for human reproduction by showing that a multiparous woman lacks a KIR2DL4 gene.

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“…The polymorphisms that alter the protein sequence include 5 alleles: G*0101, G*0103, G*0104, G*0105N and G*0106. A polymorphic 1 bp deletion of a cytosine residue at codon 130 results in a null allele (G*0105N), which does not encode functional HLA-G1 or-G5 protein isoforms [31]. This null mutation has been associated with an increased risk for recurrent miscarriage [32,33].…”

Section: Evaluation Of Hla-g Gene Polymorophismsmentioning

confidence: 99%

HLA-G and its role in implantation (review)

Roussev

Coulam

2007

J Assist Reprod Genet

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Background Human leukocyte antigen G (HLA-G) is thought to play a key role in implantation by modulating cytokine secretion to control trophopblastic cell invasion and to maintain a local immunotolerance. Method of study The literature is reviewed to provide a description of the genetic background, properties of the protein, and the function of HLA-G. Data are presented on potential clinical applications of HLA-G including the use of evaluation of HLA-G gene polymorphisms in the diagnosis of patients experiencing recurrent pregnancy loss and evaluation and testing of soluble HLA-G (sHLA-G) in embryo culture media for the selection of embryos for transfer after in vitro fertilization (IVF). Results The literature supports a central role of HLA-G for successful implantation. Of couples experiencing recurrent pregnancy loss, 32% demonstrated the -1725G HLA-G polymorphism. Our data showed that when embryos were selected for transfer after IVF based on culture media concentrations of sHLA-G≥2 U/ml and good morphologic grade, a 65% pregnancy rate compared with a 0% pregnancy rate in those with <2 U/ml sHLA-G. Conclusions HLA-G is important for successful implantation in human beings. The HLA-G -725 promoter polymorphism is a risk factor for recurrent miscarriage. Measurement of sHLA-G in embryo culture media can help select embryos for transfer after IVF allowing fewer embryos to be transferred in an attempt to lower multiple gestation rates.

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HLA-G1 protein expression is not essential for fetal survival

Cited by 172 publications

References 18 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

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

HLA-G and its role in implantation (review)

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