Improving tissue matching between organ donor and recipient
Although many successful transplant operations are carried out each year in the UK, ensuring good tissue compatibility between donor and recipient remains a problem. Specialised tissue compatibility proteins on the cells of the donor organ are often recognised as foreign by receptors on the recipient’s immune cells, a process that ultimately leads to organ rejection. Currently when organs are allocated to recipients, doctors try to ensure that the donor and recipient have as many of these compatibility proteins in common (matching) as possible to give the best chance of a successful transplant. However, because there are multiple forms of these proteins and the combinations differ between individuals, exact tissue matches are difficult to find and therefore most recipients receive a mismatched organ. As a result, high-dose complex anti-rejection medication is needed to reduce the risk of organ rejection, which has many often life-threatening side-effects.
In Theme 5 we are trying to improve our understanding of the structure and function of the compatibility proteins on the donor organs and of the receptors on the recipient’s immune cells. We are developing new genetic tests to enable fast and accurate characterisation of these proteins in donors and recipients. We are also using computer models to study the physical properties of the proteins to help predict which protein mismatches do not cause problems for the recipient and which result in damaging immune responses. We hope to identify donor–recipient tissue mismatch combinations that are less likely to lead to rejection and organ failure and aim to develop a new matching procedure that will improve organ allocation.
In addition, we also want to better understand how tissue mismatches influence the risk of development of infections and organ rejection after transplantation. We are particularly interested in studying the role of antibodies made by the recipient’s immune system against the donor compatibility proteins and hope to be able to identify which of these antibodies are most harmful to the function of the transplanted organ. This might lead to better monitoring after transplantation and enable earlier intervention before development of irreversible damage to the donated organ.