Human Leukocyte Antigen (HLA)-G and HLA-E gene polymorphisms and severe preeclampsia
(2014) MOBT15 20132Degree Projects in Molecular Biology
- Abstract
- In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class lb protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unfore seen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact. its expression pattern is primarily limited to extravillous cytotrophoblast cells at the matemal fetal intarface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. lt is these unique features that make HLA-G differ from its highly polymorphic... (More)
- In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class lb protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unfore seen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact. its expression pattern is primarily limited to extravillous cytotrophoblast cells at the matemal fetal intarface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. lt is these unique features that make HLA-G differ from its highly polymorphic HLA class la counterparts, the HLA-A, -B. and -C molecules. lts function, seemingly diverse, is typically receptor-mediated, and invalves intaractions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G playsan important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be invalved in maehanisms in reproductive immunology even betare conception because HLA-G can be detected in the genital tract and in the blood of non-pregnantwomen, and is present in seminal fluid from men. In addition, HLA-G expres sion has been found in the pre-implantad embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is Iikeiy to be important. Furthermore, this review presentsimportant aspects of HLA-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy. (Less)
- Popular Abstract
- Preeclampsia - When the mother’s immune system reacts on her fetus
Preeclampsia is a disease of late pregnancy that affects the mother to be. It has been referred to as the “disease of theories” because it presents with broad symptoms, like elevated blood pressure and increased level of protein in the urine, and the origin of preeclampsia is thus not clearly understood. One thing is certain though; the only cure is delivery of the baby.
Preeclampsia is one of the main causes of maternal mortality and morbidity and affects 2-8% of pregnancies. Even though it has been the focus of intense investigation, the cause of the disease is not known. However research has shown that the immune system of the mother is involved. The fetus can be... (More) - Preeclampsia - When the mother’s immune system reacts on her fetus
Preeclampsia is a disease of late pregnancy that affects the mother to be. It has been referred to as the “disease of theories” because it presents with broad symptoms, like elevated blood pressure and increased level of protein in the urine, and the origin of preeclampsia is thus not clearly understood. One thing is certain though; the only cure is delivery of the baby.
Preeclampsia is one of the main causes of maternal mortality and morbidity and affects 2-8% of pregnancies. Even though it has been the focus of intense investigation, the cause of the disease is not known. However research has shown that the immune system of the mother is involved. The fetus can be compared to a transplanted organ. It is genetically different from the mother because it is at product of both the mother and the father, and the fetus is thus foreign in the eyes of the mother’s immune system. The immune system of the mother nevertheless tolerates the fetus. In the placenta, where the cells of the fetus meet the cells of the mother, a unique molecule, Human Leukocyte Antigen-G (HLA-G), from the fetus is expressed. This molecule has an immune down-regulating effect and interacts with the cells of the mother’s immune system to keep them in check. The fetal gene that codes for HLA-G encompasses several inter-individual variations, some of which has been proved to reduce the expression level of the fetal HLA-G molecule. A certain combination of these variations in the fetal HLA-G gene is hypothesized to increase the risk of preeclampsia in the mother. If this is the case, a genetic test could indicate the risk of developing preeclampsia and/or be used as a diagnostic marker.
DNA samples from 75 newborns born by mothers with severe preeclampsia
In Denmark a biobank, which is a bank with biological material like blood, has been established during a 15-year period, containing blood samples from the mother and her newborn from 100.000 pregnancies. In addition, clinical data concerning the health of the mother and her baby is available. From this biobank we received 233 DNA samples from mother and newborn where the mother had been diagnosed with severe preeclampsia. An equal amount of controls were retrieved. Not all of the samples have been analyzed yet so the results are not conclusive. In my project I looked at DNA samples from 75 newborns born by mothers with severe preeclampsia (cases) and 75 newborns born by healthy mothers (controls). I sequenced (determined the genetic code of) the HLA-G gene in each of the 150 newborns and compared the variations in the cases with the variations in the controls. I found no significant difference between the overall fetal HLA-G gene variation combinations in the cases compared to the controls. However, a set of specific variations, was encountered twice as frequent in the control group compared to the case group, and can perhaps comprise a protective effect of the fetus towards the immune system of the mother. The further analyses will shed some light on this.
Advisor: Thomas V. F. Hviid, Department of Clinical Biochemistry,
Copenhagen University Hospital, Roskilde, Denmark.
Master’s Degree Project 60 credits in Molecular Biology, Medical Biology 2014
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/4678933
- author
- Lynge Nilsson, Line
- supervisor
- organization
- course
- MOBT15 20132
- year
- 2014
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 4678933
- date added to LUP
- 2014-09-24 14:53:53
- date last changed
- 2014-09-24 14:53:53
@misc{4678933,
abstract = {{In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class lb protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unfore seen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact. its expression pattern is primarily limited to extravillous cytotrophoblast cells at the matemal fetal intarface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. lt is these unique features that make HLA-G differ from its highly polymorphic HLA class la counterparts, the HLA-A, -B. and -C molecules. lts function, seemingly diverse, is typically receptor-mediated, and invalves intaractions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G playsan important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be invalved in maehanisms in reproductive immunology even betare conception because HLA-G can be detected in the genital tract and in the blood of non-pregnantwomen, and is present in seminal fluid from men. In addition, HLA-G expres sion has been found in the pre-implantad embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is Iikeiy to be important. Furthermore, this review presentsimportant aspects of HLA-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy.}},
author = {{Lynge Nilsson, Line}},
language = {{eng}},
note = {{Student Paper}},
title = {{Human Leukocyte Antigen (HLA)-G and HLA-E gene polymorphisms and severe preeclampsia}},
year = {{2014}},
}