Inducing tolerance to blood group antigens in sickle cell disease - School of Cellular and Molecular Medicine and Bristol Institute for Transfusion Sciences, NHS Blood and Transplant
Sickle-cell disease (SCD) is a hereditary blood disorder, caused by an abnormality in haemoglobin S (Hb S). Almost 300,000 children are born with a form of sickle-cell disease every year. Chronic blood transfusions are often used in the management of sickle-cell disease to alleviate anaemia and to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells. However, development of autoantibodies and alloantibodies to red cells is a major complication in SCD, due in part to donor–recipient genetic or racial disparity. Many patients will go on to develop additional antibodies, complicating the search for compatible donor cells and leading to delays in treatment. New strategies are required to reduce alloimmunisation and increase the availability of red cells for the treatment of these patients.
Alloimunisation has been shown to be greater in individuals with thalassemia who received their first transfusion after 3 years of age compared to infants transfused prior to this age. In the first year of life infants are sufficiently immature for the induction of immune tolerance. Chronic transfusions begun during this time may lead to lower immunisation rates. Consequently, it may be possible to induce tolerance to red blood cell (RBC) antigens by exposing young infants to these cells; however, this has not been tested in SCD patients. RBC shed cell-membrane-derived vesicles containing damaged cellular components. The vesicles are taken up by immune cells that digest and dispose of this cellular debris. Patients with SCD shed more vesicles and it may be possible to use these as a means of inducing immune tolerance to blood group antigens. This project will investigate induction of tolerance using plasma from SCD patients and the mechanisms underlying it.
The PhD student will join the research team of Dr Allison Blair and work closely with the research team of Professor David Anstee.
Candidates will be expected to have at least an upper-second (2.1) class degree or equivalent in a relevant discipline (Cellular or Molecular Biology, Immunology, Biochemistry). Prior interest or research experience in cell culture and molecular biology techniques will be advantageous.
Please make an online application for this project at www.bris.ac.uk/study/postgraduate/apply. Please select Cellular and Molecular Medicine on the Programme Choice page and enter details of the studentship when prompted in the Funding and Research Details sections of the form.
This is a 4 year funded PhD studentship; funding includes a standard stipend. Funds are also available for tuition fees at 'home' (UK/EEA) rates. Note that UK/EEA Residency legal requirements apply.
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