Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Craenmehr, M.H.C.; Nederlof, Iris; Cao, Milo; Drabbels, Jos J.M.; Spruyt-Gerritse, Marijke; Anholts, J.; Kapsenberg, Hanneke; Stegehuis, Janine A; Keur, Carin van der; Fasse, Esther; Haasnoot, Geert W.; Hoorn, Marie-Louise van der; Claas, Frans H.J.; Heidt, Sebastiaan; Eikmans, Michael

doi:10.3390/ijms20030625

Cited by 20 publications

(27 citation statements)

References 39 publications

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“…In particular, in vitro studies on JEG-3 cells have suggested that over-expression of miR-133a may be responsible for decreased HLA-G expression, providing evidence that miR-133a regulates HLA-G expression by reducing translation and could be involved in the pathogenesis of unexplained RM [39]. Consistently, HLA-G was found to be increased in term placentas of women with a previous history of RM compared to women without previous adverse pregnancy outcomes [40]. On the other hand, in a recent meta-analysis, no differences in terms of uterine NK levels have been found between women with RM and normal pregnancy outcomes [41].…”

Section: Miscarriagementioning

confidence: 89%

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

Tersigni

Meli

Neri

et al. 2020

IJMS

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The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.

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Section: Miscarriagementioning

confidence: 89%

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

Tersigni

Meli

Neri

et al. 2020

IJMS

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“…Accordingly, HLA-G*01:01:02/01:01:02 genotype concordance between mother and her child was shown to increase the risk of oral infection of the child by any HPV genotype and/or HR-HPV genotypes (OR 2.45) [23]. This raised the possibility that oral HPV infections detected in young women might be determined by their mother's HLA-G status [25].…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have assessed the associations between HLA-G polymorphism and female reproductive health [25,26]. HLA-G seems to play a major role as a suppressor of the immune response at the maternal-fetal interface as well as in placental angiogenesis [27].…”

Section: Discussionmentioning

confidence: 99%

“…Craenmehr et al reported HLA-G over-expression in the full-term placenta of the women with a history of recurrent miscarriages (OR = 6.67) [25]. In another study, HLA-G gene alleles *0106, *010106, *01010106 and *0105N were signi cantly higher in patients with embryonic implantation failure on infertility treatments [26] In the present study, we could not con rm these results on HLA-G alleles, but we showed an association with HLA-G G*01:01:02/01:04:01 genotype and risk of both infertility and undergoing treatments for infertility (OR = 5.06 and OR = 9.07, respectively).…”

Section: Discussionmentioning

confidence: 99%

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HLA-G Polymorphism Impacts the Outcome of Oral HPV Infections in Women

Jaakola¹,

Roger

Faucher

et al. 2021

Preprint

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Purpose: Human leukocyte antigen (HLA)-G may have an important role in the natural history of human papillomavirus (HPV) infection. Our aim was to evaluate the role of HLA-G in the outcome of genital and oral HPV infections in women. Methods: Analyses included 306 women from the Finnish Family HPV-study and were followed-up for six years. Genital and oral samples were tested for 24 different HPV types with multiplex HPV genotyping. HLA-G alleles were determined through direct DNA-sequencing. Unconditional logistic regression was used to determine the associations between HLA-G genotypes and HPV infection outcomes.Results: Nine HLA-G alleles were identified. Most common HLA-G genotypes were the wild type G*01:01:01/01:01:01 (31.3%) followed by G*01:01:01/01:01:02 (26.8%). G*01:01:01/01:01:01 genotype was associated with increased risk of oral HPV infections by any HPV type or single-type with OR=1.86 (95% CI 1.14-3.04) and 2.22 (95% CI 1.14 - 3.71), respectively. G*04:01+ allele and the G*01:01:01/01:04:01 genotype both protected from any and single oral HPV infections; OR=0.46 (95% CI 0.23-0.89) and 0.53 (95% CI 0.23-0.97), respectively. G*01:01:02/01:04:01 genotype increased significantly the risk of infertility and its treatments, with respective OR= 5.06 (95% CI 1.22-21.02) and OR=9.07 (95% CI 1.22-39.50). Both HLA-G alleles and genotypes showed several significant associations with the outcomes of oral HPV infections, but none of them had any impact on the outcomes of genital HPV infections in these women. Conclusion: The host HLA-G genotypes appear to impact the outcomes of oral HPV infections in women but have little if any effect on genital HPV status or infection outcomes.

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“…This molecule inhibits immune responses and induces the production of inhibitory and regulatory cells [9]. Changes in HLA-G ex-pression have been reported in the tissues of RPL patient [13]. Nucleotide changes in the promoter may affect HLA-G expression level by altering binding affinity that target transcription factors [16].…”

Section: Introductionmentioning

confidence: 99%

Haplotype Effect of Two Human Leukocyte Antigen-G Polymorphisms of rs1736933 and rs2735022 on the Recurrent Pregnancy Loss

Najafi

Khalaj‐Kondori

Feizi

et al. 2020

JQUMS

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Background: Recurrent Pregnancy Loss (RPL) is a multifactorial disease that affects 1-3% of couples. Since Human Leukocyte Antigen-G (HLA-G) gene is involved in fetal maternal immune tolerance, mutations in the HLA-G gene can affect the success rate of pregnancy. Objective: The present study aims to investigate the haplotype effect of rs1736933 and rs2735022 polymorphisms found in the HLA-G gene on the RPL. Methods In this case-control study, participants were 100 women with RPL and 80 women with normal fertility in northwestern Iran. The HLA-G gene promoter was amplified by Polymerase Chain Reaction (PCR) method and sequenced. The genotype and allele frequencies of the two polymorphisms were compared between the two groups by using t-test in SPSS software version 22. Haplotype analysis was performed using PHASE 2.1 and Haploview 4.2 applications Findings: C allele and CC genotype in rs2735022 polymorphism and the G allele and GG genotype in rs1736933 polymorphism showed a significant association with the RPL (P<0.05). Frequency of haplotypes AA, AC, GA, GC were 0.72, 0.23, 0.01, 0.03 in patients and 0.39, 0.01, 0.02, 0.59 in the control group (P<0.05). The linkage disequilibrium score was 94. Conclusion: Analysis of GC haplotype in rs2735022 and rs1736933 polymorphisms of the HLA-G gene can be helpful in genetic studies of women with RPL.

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Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Cited by 20 publications

References 39 publications

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

HLA-G Polymorphism Impacts the Outcome of Oral HPV Infections in Women

Haplotype Effect of Two Human Leukocyte Antigen-G Polymorphisms of rs1736933 and rs2735022 on the Recurrent Pregnancy Loss

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