Theme 3 is led by transplant surgeon and scientist Mr Vasilis Kosmoliaptsis (Cambridge) and focuses on improving long-term outcomes for transplant patients. Much of the research aims to improve understanding of tissue matching between donors and recipients.
Many successful transplant operations are carried out each year in the UK. However, trying to ensure that the tissue of the donor and recipient are compatible (match) can be a problem. Specialised tissue compatibility proteins on the cells of the donor organ are often recognised as foreign by the recipient’s immune cells. If this happens it can lead to organ rejection.
Currently, before organs are allocated, doctors try to make sure that the donor and recipient have as many of the compatibility proteins in common as possible. This process is known as tissue matching. A good match will give the best chance of a successful transplant. However, exact tissue matches are difficult to find. Therefore, most recipients receive a mismatched organ. As a result, strong anti-rejection medication is needed to reduce the risk of organ rejection. This medication can have unwanted side-effects.
Research in this theme aims to improve our understanding of the compatibility proteins on the donor organs and the receptors on the recipient’s immune cells. It is these receptors that can recognise the donor organ as foreign. If this happens, the body’s immune system may try to reject the organ. New tests are being developed so that these proteins can be identified quickly and more accurately. Computer models are being used to study the proteins. These will help to predict which protein mismatches do not cause problems for the recipient and which result in damaging immune responses. The aim is to identify tissue mismatch combinations that are less likely to lead to rejection and organ failure. Patients with low-risk tissue mismatch combinations may need less medication to remain rejection free. This reduces the risk of getting side-effects from the medication. This work can also help to develop a new tissue matching procedure that improves organ allocation.
We are doing other studies to help us understand better how tissue mismatches influence the risk of developing 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. We want to identify which of these antibodies are most harmful to the function of transplanted organs. This might lead to better monitoring after transplantation and help medical staff to start treatment earlier before the donated organ is irreversibly damaged.
Patient impact
- Better understanding of tissue matching can improve long-term transplant outcomes for patients.
- It can also improve access to transplantation. If we understand better which tissue mismatches do not cause problems, we can allocate organs to patients currently considered poor tissue matches.
- Similarly, if we can better detect and characterise antibodies made by the recipient’s immune system we may be able to improve assessment of the risk associated with a particular donor organ before transplantation. This could enable early intervention after transplantation, before irreversible injury to the organ.
