Donor-recipient KIR/HLA mismatches and organ transplant outcomes
Research type
Research Study
Full title
Investigation of the clinical significance of donor-recipient Killer Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) mismatches in kidney and liver transplantation.
IRAS ID
152768
Contact name
Vasilis Kosmoliaptsis
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and The University of Cambridge
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Despite improvements in early graft survival after organ transplantation, 30% of kidneys and 40% of livers fail within 10 years of transplant often from molecular processes that are not well understood. In particular, organ rejection and post-transplant opportunistic infections represent major barriers to improving long-term transplant outcomes.
A population of immune cells, called Natural-Killer (NK) cells, have been implicated in both acute and chronic organ rejection and in antiviral immunity after transplantation. However, their significance for transplant outcomes is poorly defined. The interaction between recipient NK cell Killer-Immunoglobulin-like Receptors (KIR) and Human-Leukocyte-Antigens (HLA) expressed on donor tissue is of principal importance. Until recently, the genetic content of the KIR complex was difficult to define because of limitations in our ability to directly determine (type) the KIR genes. We have recently developed an automated KIR typing system (Genome Research 2012;22:1845) that enables accurate and rapid assessment of the presence or absence of all individual KIR genes and their copy number, providing the opportunity to study large patient cohorts.
We aim to retrospectively determine the KIR type of a large cohort of deceased-donor organ recipients and the HLA type (if not already known) of their donors using archived tissue held by our tissue typing laboratory. Our aim is to do this for 1000 kidney and 500 liver transplants to determine definitively the impact of KIR/HLA mismatching on transplant outcomes (rejection and graft survival), using follow-up data from NHS Blood and Transplant. We will also examine the effect of KIR genotype on susceptibility to post-transplant cytomegalovirus infection (a major source of morbidity and mortality).
We anticipate that this study will improve our understanding of the impact of NK cell KIR/HLA mismatching on solid-organ transplant outcomes and may help improve donor-recipient matching and inform future deceased-donor allocation policy to maximise the benefits of transplantation.
REC name
London - Harrow Research Ethics Committee
REC reference
16/LO/0434
Date of REC Opinion
25 Feb 2016
REC opinion
Favourable Opinion