title: The many faces of human leukocyte antigen-G: relevance to the fate of pregnancy.
abstract: Pregnancy is an immunological paradox, where fetal antigens encoded by polymorphic genes inherited from the father do not provoke a maternal immune response. The fetus is not rejected as it would be theorized according to principles of tissue transplantation. A major contribution to fetal tolerance is the human leukocyte antigen (HLA)-G, a nonclassical HLA protein displaying limited polymorphism, restricted tissue distribution, and a unique alternative splice pattern. HLA-G is primarily expressed in placenta and plays multifaceted roles during pregnancy, both as a soluble and a membrane-bound molecule. Its immunomodulatory functions involve interactions with different immune cells and possibly regulation of cell migration during placental development. Recent findings include HLA-G contributions from the father and the fetus itself. Much effort has been put into clarifying the role of HLA-G during pregnancy and pregnancy complications, such as preeclampsia, recurrent spontaneous abortions, and subfertility or infertility. This review aims to clarify the multifunctional role of HLA-G in pregnancy-related disorders by focusing on genetic variation, differences in mRNA stability between HLA-G alleles, differences in HLA-G isoform expression, and possible differences in functional activity. Furthermore, we highlight important observations regarding HLA-G genetics and expression in preeclampsia that future research should address.
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, 7-13 Køgevej, 4000 Roskilde, Denmark.
authors.forename: Mette
authors.identifier: 0000-0002-8036-3519
authors.initials: M
authors.lastname: Dahl
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, 7-13 Køgevej, 4000 Roskilde, Denmark.
authors.forename: Snezana
authors.initials: S
authors.lastname: Djurisic
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, 7-13 Køgevej, 4000 Roskilde, Denmark.
authors.forename: Thomas Vauvert F
authors.initials: TV
authors.lastname: Hviid
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D059951:HLA-G Antigens / Q000502:physiology*; D006801:Humans; D009928:Organ Specificity / Q000235:genetics; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000209:etiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D011256:Pregnancy Outcome; D021381:Protein Transport
chemical_list: D059951:HLA-G Antigens
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