Current national and international organ allocation algorithms seek to minimise the number of HLA mismatches between donor and recipient. However, the extensive polymorphism of the HLA system and the need to balance often competing clinical and societal factors makes exact matches difficult to achieve and, therefore, most recipients receive HLA mismatched grafts. As a consequence, HLA incompatibilities are common, often resulting in heavier immunosuppression drug therapy (increasing morbidity and mortality), in the development of antibody-mediated organ rejection, and in recipient sensitisation that can severely limit access to repeat transplantation (often necessary in children and young adults). Underpinned by our studies in HLA immunogenicity and using computational methods (e.g. 3D electrostatic similarity calculations based on HLA structural data; in silico peptide docking, T- and B-cell epitope prediction), our research aims to optimise histocompatibility by identifying donor-recipient HLA combinations that are less likely to lead to rejection and graft failure. In collaboration with NHS Blood and Transplant, we aim to develop a novel HLA matching algorithm to improve access to and outcomes after kidney transplantation.

In haematopoietic cell transplantation (HCT) the requirements for donor-recipient HLA matching are more stringent than kidney transplantation. We have shown that donor HLA alleles with high physicochemical disparity to recipient HLA increase the risk of acute graft-versus-host disease after HCT. In collaboration with the British Society of Blood and Marrow Transplantation, our research aims to develop HLA matching algorithms that enhance options for donor selection and improve outcomes for patients in need of allogeneic HCT.