NIV Congres

Natural Killer (NK) cells are critical regulators of anti-viral immune reactions alongside the adaptive immune response. We hypothesized that NK cells are crucial in the anti-viral response after renal transplantation, and either directly or indirectly affect the allo-immune response. NK cell express Killer Immunoglobulin-like Receptors (KIR), which specifically recognize HLA class I antigens on target cells. These KIR/HLA interactions contribute to the complex balance between activating and inhibitory receptors signalling which determine whether or not NK cell effector functions are initiated. We studied the association of NK cell KIR and HLA genotype with risk of Cytomegalorvirus (CMV) primary infection/disease and rejection episodes after renal transplantation. Renal transplant patients between 2002 and 2011 at UMC St. Radboud Nijmegen were included and organized into four groups defined by the CMV sero-status of the recipient (R) and donor (D). Inclusion criteria were >19yrs, first transplant, immunosuppressive regimen (Tacro/MMF/Pred). First, we analyzed the association of KIR genotype and risk of CMV disease in the R-/D+ cohort. A total of 90 R-/D+ patient-recipient pairs were included in this cohort of which about half received the kidney from a living donor. In this cohort of 90 donor-recipient pairs the incidence of CMV disease was 43.3% and the rejection rate was 30% in the first year of transplantation. The average time to CMV disease was 142 ± 45 days after transplantation. KIR typing results revealed a similar gene distribution in our R-/D+ recipients as compared to previous data on European renal transplant cohorts. The frequency of KIR haplotypes AA and BA/BB (BX) was 31% and 69%, respectively. Preliminary risk analysis showed no association between recipient’s HLA Bw4/Bw6 and C1/C2 epitopes and the risk of CMV disease. CMV disease was not a risk factor for the rejection episodes observed in this cohort. Neither were the recipient ‘s KIR haplotypes and HLA Bw4/Bw6 and C1/C2 epitopes significantly correlated with the observed rejection episodes. However, in contrast to some earlier studies, recipients with the KIR AA haplotype showed a better, albeit not statistically significant, outcome in CMV disease incidence when compared to recipients with the KIR BX haplotype. Analysis of additional cohorts and functional studies should provide us with a rationale for our observed findings.