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Journal of Immunology Research - Volume 2014 2014, Article ID 591489, 11 pages -

Review ArticleDepartment of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology CIRRI, Copenhagen University Hospital Roskilde and Roskilde Hospital, 7-13 Køgevej, 4000 Roskilde, Denmark

Received 9 December 2013; Accepted 17 January 2014; Published 4 March 2014

Academic Editor: Roberta Rizzo

Copyright © 2014 Mette Dahl et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.

Author: Mette Dahl, Snezana Djurisic, and Thomas Vauvert F. Hviid



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