Telomeric rather than centromeric activating KIR genes protect from cytomegalovirus infection after kidney transplantation

Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer-cell immunoglobulin-like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44-0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60-1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.