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

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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Acknowledgements

The Swiss Transplant Cohort Study is funded by a grant from the Swiss National Science Foundation (3347CO-108795). This work was supported by the Swiss National Science Foundation (PP00P3_128461/1 to MS, and 31003A_135677/1 to CH). This work was supported by the Freiwillige Akademische Gesellschaft, Basel.

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Gonzalez, A., Schmitter, K., Hirsch, H. et al. KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients. Genes Immun 15, 495–499 (2014). https://doi.org/10.1038/gene.2014.39

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