The Role of KIR2DS4 Polymorphisms in BK Virus and Acute Rejection Following Renal Transplantation
Patrick Trotter1, Jessica Padley2, Keziah Crick1, Jyothi Jayaraman3, James Traherne3, John Trowsdale3, Menna Clatworthy2.
1Department of Surgery, University of Cambridge, Cambridge, United Kingdom; 2Department of Medicine , University of Cambridge, Cambridge, United Kingdom; 3Department of Pathology, University of Cambridge, Cambridge, United Kingdom
Introduction: Natural Killer (NK) cells have been implicated in the pathogenesis of rejection, and their activation may be modulated by engagement of Killer cell Immunoglobulin-like Receptors (KIRs). The KIR gene is highly polymorphic and the inhibitory KIRs are activated in response to self HLA (‘missing-self hypothesis’). Polymorphisms in KIR genes have been associated differential outcomes in infection and pregnancy. To date, the impact of KIR genotype on immune responses in renal transplantation has not been fully explored. We aimed to interrogate activating KIR2DS4 polymorphisms in kidney transplant recipients and to determine whether variation in this gene was associated with susceptibility to BK viraemia (BKV) or acute rejection.
Materials and Methods: Genomic DNA was obtained from n=1010 kidney transplant recipients at a single centre between 2008-2014 and KIR2DS4 polymorphisms analysed via sequence specific primer polymerase chain reaction (SSP PCR).
Results: 1203 renal transplants were performed at our unit between 2008-2014, of which 157 (12.2%) developed BKV viraemia, 145 (12.0%) developed acute rejection (both cellular and antibody mediated) and 35 (2.9%) renal recipients developed both BKV and acute rejection. DNA was available or could be extracted from n=1010 (83.9%) of these recipients. The KIR2DS4 full length polymorphism was more common in renal recipients of Asian and Black ethnicities compared to White (17.3% and 37.9% vs. 13.5%), whereas the 22-base pair deletion variant was more commonly observed in the White renal recipient population compared to the black population (55.3% vs. 20.7 %). No KIR2DS4 polymorphism was found to be significantly associated with BK viraemia (p=0.214) or with acute rejection (p=0.546).
Conclusions: KIR2DS4 polymorphisms do not significantly influence susceptibility to BKV or acute rejection in renal transplant recipients. However, the KIR locus is one of the most complex regions in the human of genome and we are currently exploring how other KIR polymorphisms influence transplant outcomes.
National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU)in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT).
