Soluble HLA‐G levels in seminal plasma are associated with HLA‐G 3′UTR genotypes and haplotypes

Craenmehr, M.H.C.; Haasnoot, Geert W.; Drabbels, Jos J.M.; Spruyt-Gerritse, Marijke; Cao, Milo; Keur, Carin van der; Kapsenberg, J.M.; Uyar‐Mercankaya, Merve; Beelen, Els van; Meuleman, Tess; Hoorn, Marie-Louise van der; Heidt, Sebastiaan; Claas, Frans H.J.; Eikmans, Michael

doi:10.1111/tan.13628

Cited by 14 publications

(11 citation statements)

References 31 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Haplotypes and diplotypes containing UTR-1 have been associated with high levels of plasma sHLA-G, those containing UTR-5 and UTR-7 with low levels of sHLA-G, and finally, alleles containing UTR-2, UTR-3, UTR-4, and UTR-6 with medium levels of sHLA-G (51). These results were confirmed in other biological fluids as the highest levels of HLA-G in seminal plasma have been detected in the presence of homozygosis for UTR-1 and UTR-3 (52). Our group defined the association of specific UTRs with the expression of HLA-G1 in a specific subset of tolerogenic DC, termed DC-10, inducible in vitro in the presence of IL-10 (53) and present in vivo (54).…”

Section: Association Hla-g Genotype/phenotypesupporting

confidence: 75%

HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives

Amodio

Gregori

2020

Front. Immunol.

View full text Add to dashboard Cite

The non-classical HLA-G is a well-known immune-modulatory molecule. In physiological condition, HLA-G surface expression is restricted to the maternal-fetal interface and to immune-privileged adult tissues, whereas soluble forms of HLA-G are detectable in various body fluids. HLA-G can be de novo expressed in pathological conditions including tumors, chronic infections, or after allogeneic transplantation. HLA-G exerts positive effects modulating innate and adaptive immune responses and promoting tolerance, or detrimental effects inducing immune escape mechanisms. HLA-G locus, in contrast to classical HLA class I gene, is highly polymorphic in the non-coding 3 ′ untranslated region (UTR) and in the 5 ′ upstream regulatory region (5 ′ URR). Variability in these regions influences HLA-G expression by modifying mRNA stability or allowing posttranscriptional regulation in the case of 3 ′ UTR or by sensing the microenvironment and responding to specific stimuli in the case of HLA-G promoter regions (5 ′ URR). The influence of genetic variations on the expression of HLA-G makes it an attractive biomarker to monitor disease predisposition and progression, or response to therapy. Here, we summarize the current knowledge, efforts, and obstacles to generate a general consensus on the correlation between HLA-G genetic variability, protein expression, and disease predisposition. Moreover, we discuss perspectives for future investigation on HLA-G genotype/expression in association with disease predisposition and progression.

show abstract

Section: Association Hla-g Genotype/phenotypesupporting

confidence: 75%

HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives

Amodio

Gregori

2020

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…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 )]. Finally, four studies were included in the quantitative meta-analysis ( 35 , 77 – 79 ). The flow diagram of selecting studies for systematic review and meta-analysis is shown in Figure 1 .…”

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.

View full text Add to dashboard Cite

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.

show abstract

“…HLA-G is oligomorphic and has seven isoforms, of which some are membrane-bound (HLA-G1 to -G4), and others are secreted as a soluble form (sHLA-G5 to -G7) (142). Several polymorphisms in the untranslated region (UTR) of the HLA-G gene have been associated with lower sHLA-G levels in both blood and seminal plasma (143,144). In both PE and RPL, a reduction in serum sHLA-G levels has been observed compared to healthy control women (145)(146)(147)(148).…”

Section: Hla-gmentioning

confidence: 99%

Regulatory T Cells in Pregnancy: It Is Not All About FoxP3

et al. 2020

Self Cite

View full text Add to dashboard Cite

In pregnancy, the semi-allogeneic fetus needs to be tolerated by the mother's immune system. Regulatory T cells (Tregs) play a prominent role in this process. Novel technologies allow for in-depth phenotyping of previously unidentified immune cell subsets, which has resulted in the appreciation of a vast heterogeneity of Treg subsets. Similar to other immunological events, there appears to be great diversity within the Treg population during pregnancy, both at the maternal-fetal interface as in the peripheral blood. Different Treg subsets have distinct phenotypes and various ways of functioning. Furthermore, the frequency of individual Treg subsets varies throughout gestation and is altered in aberrant pregnancies. This suggests that distinct Treg subsets play a role at different time points of gestation and that their role in maintaining healthy pregnancy is crucial, as reflected for instance by their reduced frequency in women with recurrent pregnancy loss. Since pregnancy is essential for the existence of mankind, multiple immune regulatory mechanisms and cell types are likely at play to assure successful pregnancy. Therefore, it is important to understand the complete microenvironment of the decidua, preferably in the context of the whole immune cell repertoire of the pregnant woman. So far, most studies have focused on a single mechanism or cell type, which often is the FoxP3 positive regulatory T cell when studying immune regulation. In this review, we instead focus on the contribution of FoxP3 negative Treg subsets to the decidual microenvironment and their possible role in pregnancy complications. Their phenotype, function, and effect in pregnancy are discussed.

show abstract

Soluble HLA‐G levels in seminal plasma are associated with HLA‐G 3′UTR genotypes and haplotypes

Cited by 14 publications

References 31 publications

HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives

HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives

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

Regulatory T Cells in Pregnancy: It Is Not All About FoxP3

Contact Info

Product

Resources

About