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

Journal Paper/Review - Jul 10, 2014

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Gonzalez A, Schmitter K, Hirsch H, Garzoni C, van Delden C, Boggian K, Mueller N, Berger C, Villard J, Manuel O, Meylan P, Stern M, Hess C. KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients. Genes Immun 2014; 15:495-9.
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Journal Paper/Review (English)
Journal
Genes Immun 2014; 15
Publication Date
Jul 10, 2014
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Issn Electronic
1476-5470
Pages
495-9
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Brief description/objective

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.