Dahl, Mette2; Djurisic, Snezana2; Hviid, Thomas Vauvert F3
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Relevance to the Fate of Pregnancy
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.
Journal review article
Immunologic Research, 2014, Vol 2014, p. 1-11
Alleles; Alternative Splicing; Cell Membrane; Female; Gene Expression Regulation; HLA-G Antigens; Humans; Organ Specificity; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Protein Transport