KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients

A Gonzalez, K Schmitter, HH Hirsch, C Garzoni… - Genes & …, 2014 - nature.com
A Gonzalez, K Schmitter, HH Hirsch, C Garzoni, C van Delden, K Boggian, NJ Mueller…
Genes & Immunity, 2014nature.com
Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR)
genes with protection from cytomegalovirus (CMV) replication after organ transplantation.
Whether KIR-associated protection is operating in the context of primary infection, re-
activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus
at the time of transplantation with rates of CMV viremia in 517 heart (n= 57), kidney (n= 223),
liver (n= 165) or lung (n= 72) allograft recipients reported to the Swiss Transplant Cohort …
Abstract
Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n= 57), kidney (n= 223), liver (n= 165) or lung (n= 72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes—which in contrast to A haplotypes may contain multiple activating KIR genes—to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression)(hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29–0.75, P= 0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26–0.77, P= 0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22–1.53, P= 0.28). These data indicate a prominent role for KIR—and presumably natural killer (NK) cells—in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression.
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