The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

Mao, Jia; Feng, Ying; Zhu, Xiaofeng; Ma, Fang

doi:10.3390/biom13081213

Cited by 6 publications

(4 citation statements)

References 156 publications

(181 reference statements)

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“…The soluble forms (HLA-G1, -G5, -G6, and -G7) are released from the cells due to the lack of transmembrane and intracellular domains in the membranebound form. The soluble subtypes are produced by various cells, such as extravillous and villous cytotrophoblasts, chorion and amnion membranes, syncytiotrophoblasts, decidual stromal cells, fetal endothelial cells, and immune cells, in the placenta [2,3].…”

Section: Introductionmentioning

confidence: 99%

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies

Vincze,

Sikovanyecz,

Földesi

et al. 2024

Bioengineering

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Introduction: Trophoblast-derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. Human Leukocyte Antigen-G (HLA-G) belongs to the non-classical human major histocompatibility complex (MHC-I) molecule and has membrane-bound and soluble forms. HLA-G is primarily expressed by extravillous cytotrophoblasts located in the placenta between the maternal and fetal compartments and plays a pivotal role in providing immune tolerance. The aim of this study was to establish a relationship between concentrations of soluble HLA-G (sHLA-G) in maternal serum and amniotic fluid at 16–22 weeks of gestation and the sonographic measurements of fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices, were determined in 41 singleton pregnancies with no complications. The level of sHLA-G (U/mL) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: The sHLA-G levels were unchanged both in amniotic fluid and serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β = 0.63, p < 0.01). Serum sHLA-G level was significantly correlated with abdominal measurements (β = 0.41, p < 0.05) and estimated fetal weight (β = 0.41, p < 0.05). Conversely, amniotic sHLA-G level and placental perfusion (VI: β = −0.34, p < 0.01 and VFI: β = −0.44, p < 0.01, respectively) were negatively correlated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = −0.102, p < 0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator of placental function, whereas the sHLA-G level in serum can be a prognostic factor for feto-placental insufficiency.

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Section: Introductionmentioning

confidence: 99%

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies

Vincze,

Sikovanyecz,

Földesi

et al. 2024

Bioengineering

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“…HLA‐G interacts with decidual natural killer (NK) cells to induce secretion of pro‐inflammatory and pro‐angiogenic factors and may activate the NK cell aging system to promote stable cytokine secretion, support vascular remodeling of spiral arteries, and promote embryo implantation and fetal growth 17 . In addition, HLA‐G can regulate the function of decidual T cells, dendritic cells, and macrophages to maintain the balance between maternal and infant immune responses 18 …”

Section: Introductionmentioning

confidence: 99%

“…17 In addition, HLA-G can regulate the function of decidual T cells, dendritic cells, and macrophages to maintain the balance between maternal and infant immune responses. 18 Compared to HLA-G, HLA-F has received less attention, but this situation has changed recently. Initially, HLA-F was thought to be primarily expressed intracellularly, but was later demonstrated in the EVT that had invaded the maternal decidua.…”

mentioning

confidence: 99%

Association of human leukocyte antigen‐G and ‐F with recurrent miscarriage and implantation failure: A systematic review and meta‐analysis

Han,

Xia,

Zhu

et al. 2023

American J Rep Immunol

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ProblemThe immune system plays an essential role in embryonic implantation and pregnancy, but the molecular details remain controversial. In the past four decades, human leukocyte antigen (HLA)‐G and ‐F have garnered significant attention.Method of StudyMEDLINE, EMBASE, Web of Science, and the Cochrane Trials Registry were searched from their inception dates until December 2022. Studies were selected following PRISMA guidelines. Meta‐analyses were used to assess the relationship of soluble HLA‐G (sHLA‐G) and HLA‐G 3′‐untranslated region polymorphisms with recurrent miscarriage (RM) and recurrent implantation failure (RIF). Narrative synthesis was conducted to determine the association of RM with other single nucleotide polymorphisms (SNPs) and HLA‐G protein in tissues and of RIF with HLA‐F. Risk‐of‐bias was assessed using ROBINS‐I. Publication bias was assessed using Egger's and Begg's tests.ResultsFinally, 42 articles were eligible for inclusion in the systematic review (32 in the meta‐analysis; 13 in narrative synthesis). We found a significant association between the 14‐bp ins/del HLA‐G polymorphism and RM risk, but no definitive association with RIF risk. Women with RM had lower blood concentrations of sHLA‐G during pregnancy and non‐pregnancy than did controls. For women in the RIF group, no significant difference was found.ConclusionHLA‐G protein and gene expression levels may be closely related to RM. The relevance of HLA‐G to RIF is still being determined. A narrative synthesis of current studies has shown that HLA‐F is likely associated with RIF.

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“…23 HLA-G expression is restricted mainly to placental trophoblast cells and in Immuno privileged sites like thymus, cornea and pancreatic islets. 24 HLA-G expression is also found in the male reproductive system and the seminal plasma. Semen consists of spermatozoa, seminal plasma and many other components including HLA-G contributing to the tolerance against paternal antigens at the maternal fetal interface.…”

mentioning

confidence: 98%

UP‐regulated levels of sHLA‐G in women with a history of RPL in mid‐gestation presumably to achieve ongoing pregnancy

Jahan,

Bhuwalka,

Begum

et al. 2023

American J Rep Immunol

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ProblemRecurrent Pregnancy Loss (RPL) is a disorder characterized by two or more pregnancy losses within 20th week of gestation. Globally 1–5% of the couples are affected, 50% of these cases are with unknown etiology. HLA‐G, an Immuno‐modulatory molecule is a non‐classical MHC‐1 protein, expressed abundantly on extravillous trophoblastic cells, responsible for spiral artery remodeling, maintaining maternal immune tolerance and fetal growth by adjusting pro and anti‐inflammatory milieu during different gestational phases.Method of studyIn the present case‐control study CD4+HLA‐G+ tTreg cells were enumerated by flow cytometry and estimation of the circulating levels of sHLA‐G in the blood samples of 300 mid‐gestation pregnant women with (iRPL) and without history of RPL (nRPL) by Enzyme‐linked Immunosorbent assay was done. The cases included 92 primary and 58 secondary RPL casesResultsA significant reduction in number of tTregs and elevated levels of circulating sHLA‐G in iRPL (.03, 200.9) versus nRPL (.09, 90.32) was observed. Further, the primary cases showed higher circulating sHLA‐G and no difference in relation to CD4+HLA‐G+ tTregs compared to the secondary cases. Receiver operating curve (ROC) characteristics of sHLA‐G (AUC = .8) was superior to CD4+HLA‐G+ (AUC = .7) for iRPL patients over nRPL group. Conclusions: Our results are suggestive of the over‐expression of sHLA‐G which may be caused due to its shedding from surface of trophoblast as a compensatory mechanism to save the on‐going pregnancy. To realize the present outcome, studies are required on on‐going pregnancy follow‐up cases with favorable and unfavorable pregnancy outcome.

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The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

Cited by 6 publications

References 156 publications

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies

Association of human leukocyte antigen‐G and ‐F with recurrent miscarriage and implantation failure: A systematic review and meta‐analysis

UP‐regulated levels of sHLA‐G in women with a history of RPL in mid‐gestation presumably to achieve ongoing pregnancy

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