The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy

Sipak, Olimpia; Rył, Aleksandra; Grzywacz, Anna; Zimny, Małgorzata; Karakiewicz, Beata; Rotter, Iwona; Kosik-Bogacka, Danuta; Cybulski, Cezary

doi:10.3390/ijerph16091546

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…sHLA-G, a soluble molecule, can be detected in pregnant women in all three trimesters. During the first trimester, this molecule plays an important role during the implantation process as it can regulate the activity of immune cells, such as NKs and cytotoxic T lymphocytes in the decidua, ensuring antigen tolerance [ 31 ]. The maternal sHLA-G concentration in patients who delivered at term by c-section showed that its levels continue to increase as labor progresses.…”

Section: Introductionmentioning

confidence: 99%

Histocompatibility Antigen, Class I, G (HLA-G)’s Role during Pregnancy and Parturition: A Systematic Review of the Literature

Tantengco

Richardson

Lee

et al. 2021

Life

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Introduction: Immune homeostasis of the intrauterine cavity is vital for pregnancy maintenance. At term or preterm, fetal and maternal tissue inflammation contributes to the onset of labor. Though multiple immune-modulating molecules are known, human leukocyte antigen (HLA)-G is unique to gestational tissues and contributes to maternal–fetal immune tolerance. Several reports on HLA-G’s role exist; however, ambiguity exists regarding its functional contributions during pregnancy and parturition. To fill these knowledge gaps, a systematic review (SR) of the literature was conducted to better understand the expression, localization, function, and regulation of HLA-G during pregnancy and parturition. Methods: A SR of the literature on HLA-G expression and function reported in reproductive tissues during pregnancy, published between 1976–2020 in English, using three electronic databases (SCOPE, Medline, and ClinicalTrials.gov) was conducted. The selection of studies, data extraction, and quality assessment were performed in duplicate by two independent reviewers. Manuscripts were separated into three categories: 1) expression and localization of HLA-G, 2) regulators of HLA-G, and 3) the mechanistic roles of HAL-G. Data were extracted, analyzed, and summarized. Results: The literature search yielded 2554 citations, 117 of which were selected for full-text evaluation, and 115 were included for the final review based on our inclusion/exclusion criteria. HLA-G expression and function were mostly studied in placental tissue and/or cells and peripheral blood immune cells, while only 13% of the studies reported data on amniotic fluid/cord blood and fetal membranes. Measurements of soluble and membranous HLA-G were determined mostly by RNA-based methods and protein by immunostaining, Western blot, or flow cytometric analyses. HLA-G was reported to regulate inflammation and inhibit immune-cell-mediated cytotoxicity and trophoblast invasion. Clinically, downregulation of HLA-G is reported to be associated with poor placentation in preeclampsia and immune cell infiltration during ascending infection. Conclusions: This SR identified several reports supporting the hypothesized role of immune regulation in gestational tissues during pregnancy. A lack of rigor and reproducibility in the experimental approaches and models in several reports make it difficult to fully elucidate the mechanisms of action of HLA-G in immune tolerance during pregnancy.

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Section: Introductionmentioning

confidence: 99%

Histocompatibility Antigen, Class I, G (HLA-G)’s Role during Pregnancy and Parturition: A Systematic Review of the Literature

Tantengco

Richardson

Lee

et al. 2021

Life

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“…28 articles were assessed for eligibility ( 8 , 19 , 35 , 38 , 39 , 41 , 42 , 50 – 70 ). 21 articles were excluded from systematic review and meta-analysis [nine are reviews ( 38 , 51 – 58 ), nine cases are not RIF patients ( 59 – 67 ), and three studies did not measure the sHLA-G levels ( 39 , 42 , 50 )]. Four studies are excluded from quantitative analysis for reasons [three articles’ data are not available to extract for synthesis ( 8 , 68 , 69 ), one study measured sHLA-G levels in the endometrium by semi-quantitative method ( 41 )].…”

Section: Resultsmentioning

confidence: 99%

“…18 articles were assessed for eligibility. Eight articles were excluded from the systematic review [five were reviews ( 57 , 58 , 71 – 73 ), two were conference abstracts without data ( 74 ), and cases in one study were not IVF patients ( 59 )]. Six studies were excluded from the quantitative meta-analysis [three studies’ data are not available to extract for synthesis ( 19 , 41 , 75 ), three articles reported the polymorphism in only one study thus cannot be synthesized ( 8 , 70 , 76 )].…”

Section: Resultsmentioning

confidence: 99%

Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis

Zeng

2022

Front. Immunol.

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IntroductionHLA-G plays a central role in immune tolerance at the maternal-fetal interface. The HLA-G gene is characterized by low allelic polymorphism and restricted tissue expression compared with classical HLA genes. HLA-G polymorphism is associated with HLA-G expression and linked to pregnancy complications. However, the association of parental HLA-G polymorphisms with soluble HLA-G (sHLA-G) expression and their roles in recurrent implantation failure (RIF) is unclear. The study aims to systematically review the association of HLA-G polymorphisms with RIF, the association of sHLA-G expression with RIF, and the association of HLA-G polymorphisms with sHLA-G expressions in patients attending in-vitro fertilization (IVF) treatment.MethodsStudies that evaluated the association of HLA-G polymorphisms with RIF, the association between sHLA-G expression with RIF, and the association between HLA-G polymorphisms with sHLA-G expressions in patients attending IVF treatment were included. Meta-analysis was performed by random-effect models. Sensitivity analysis was performed by excluding one study each time. Subgroup analysis was performed based on ethnicity.ResultsHLA-G 14bp ins variant is associated with a lower expression of sHLA-G in seminal or blood plasma of couples attending IVF treatment. The maternal HLA-G*010101 and paternal HLA-G*010102 alleles are associated with RIF risk compared to other alleles. However, single maternal HLA-G 14bp ins/del polymorphism, HLA-G -725 C>G/T polymorphism, or circulating sHLA-G concentration was not significantly associated with RIF in the general population. HLA-G 14bp ins/ins homozygous genotype or ins variant was associated with a higher risk of RIF in the Caucasian population.DiscussionSpecific HLA-G alleles or HLA-G polymorphisms are associated with sHLA-G expression in couples attending IVF treatment. Several HLA-G polymorphisms may be related to RIF, considering different ethnic backgrounds. A combined genetic effect should be considered in future studies to confirm the association of HLA-G polymorphisms and sHLA-G expressions in relation to RIF.

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“…[ 4 ] Indeed, studies have suggested a correlation between lower sHLA-G levels in cord blood and recurrent spontaneous abortion, gestational diabetes mellitus, and preeclampsia. [ 5 6 ] Moreover, HLA-G is expressed by the thymus medulla, pancreatic islets, and cornea in the steady state; during stress, cancer, or inflammation, HLA-G expression is triggered in several tissues. [ 1 7 ]…”

Section: Introductionmentioning

confidence: 99%

Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease

Cansever

Göktaş

Arslan

et al. 2022

Saudi J Gastroenterol

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Background: Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity. Methods: We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD. Conclusions: Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.

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The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy

Cited by 7 publications

References 31 publications

Histocompatibility Antigen, Class I, G (HLA-G)’s Role during Pregnancy and Parturition: A Systematic Review of the Literature

Histocompatibility Antigen, Class I, G (HLA-G)’s Role during Pregnancy and Parturition: A Systematic Review of the Literature

Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis

Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease

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