Genetic control of HLA expression
Research type
Research Study
Full title
The genetic and biochemical control of cell surface HLA expression.
IRAS ID
242983
Contact name
Bryan Carey
Contact email
Sponsor organisation
Plymouth Hospitals NHS Trust
Duration of Study in the UK
1 years, 4 months, 30 days
Research summary
Human Leucocyte Antigens (HLA) are proteins on the surface of all cells in the human body, responsible for protecting us from disease. These proteins vary in shape between individuals and we inherit the DNA that codes for these proteins from our parents.
It is the different shape of HLA proteins that causes transplant rejection. We can make antibodies against HLA proteins that differ from our own and these antibodies can destroy the transplant.
We measure antibody against HLA proteins and use this to determine whether transplantation can proceed, but there is considerable evidence that HLA levels vary between individuals. It may be possible for a patient with antibodies to receive a transplant with an organ if it has low levels of HLA protein on the cell surface.
In order to help understand variation in HLA levels between individuals, or within the same individual over time we propose the following studies.
1. Volunteers will donate blood every 4 weeks for one year or at various times over the same day. HLA surface protein and the levels of genetic ‘instructions’ will be measured. DNA will be sequenced in the HLA region to look for other genetic controls.
2. Human umbilical vein endothelial cells (HUVECs) will be used as a model of HLA expression on kidney blood vessels. These cells can be stimulated to switch between resting and active states to measure the change in HLA expression.
Mothers attending for elective Cesarean section will be asked to donate the umbilical vein. Endothelial cells will be isolated and grown in the laboratory. Cells can be artificially stimulated to simulate cell damage and the HLA surface protein and the levels of genetic ‘instructions’ will be measured. DNA will be sequenced in the HLA region to look for controls of HLA expression.REC name
HSC REC B
REC reference
18/NI/0064
Date of REC Opinion
2 May 2018
REC opinion
Further Information Favourable Opinion