The Implication of HLA-G Molecules in Pre-eclampsia

Lene Gede, Derya Aslan, Tine Hansen, Mille Andersen & Signe Andersen

Student thesis: Termpaper

Abstract

The aim of this bachelor project is to investigate the possible immunological causes of pre-eclampsia (PE), a syndrome which affects 5-8% of all pregnancies. Pre-eclampsia is defined as hypertension and proteinuria which occurs in the second half of pregnancy. It is believed that defective trophoblast invasion leads to incomplete remodeling of maternal spiral arteries during implantation, which further leads to PE. The reason for these events and the following pathology of the syndrome has not yet been identified. One of the main theories regarding the development of PE involves the immune system and the interaction with the Human Leukocyte Antigens (HLA). Trophoblast cells express the non-classical HLA molecule, HLA-G and the classical HLA-C. Furthermore, HLA-G expression is down-regulated in pre-eclamptic pregnant women compared to healthy pregnant women. Therefore the focus in this bachelor project is whether these molecules could be implicated in the development of PE. Normally HLA-G has been reported to suppress the effect of certain immune cells, such as Natural Killer (NK) cells, wherefore a decreased expression could be undesirable in pregnancy. Different polymorphisms of HLA-G have been studied in relation to PE, and certain polymorphism in offspring and/or parents have been shown to be associated with an increased risk of PE. A well studied polymorphism is a 14 bp insertion in HLA-G that has been reported to be associated with PE as well as a decreased level of HLA-G expression in the placenta. Another polymorphism, G*0106, linked to the +14 bp allele, has also been associated with PE. In regard to HLA-C, one group of polymorphisms that leads to different interaction with desidual NK (dNK) cells has been examined, showing that this group probably is associated with an increased risk of PE, due to increased inhibition of dNK cells. Some hypothesize that activation of dNK cells is beneficial for trophoblast invasion because it results in secretion of angiogenetic factors, while others state that it is important to inhibit the dNK cells so that the cytotoxic effect is reduced. Therefore both activation and inhibition of dNK cells might play a part in PE. In conclusion, the cause of PE is found to be multifactorial, because none of the examined studies show a genetic cause or a pathway that on its own leads to PE. Instead, many mechanisms are likely to influence the development and several genes might influence a woman’s susceptibility to PE.

EducationsPharmaceutical Biology, (Bachelor/Graduate Programme) Undergraduate or graduate
LanguageEnglish
Publication date25 May 2009

Keywords

  • Pregnancy
  • Pre-eclmapsia
  • HLA
  • Immune system