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

Genes Immun. 2014 Oct;15(7):495-9. doi: 10.1038/gene.2014.39. Epub 2014 Jul 10.

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / genetics*
  • Cytomegalovirus Infections / immunology
  • Female
  • Haplotypes
  • Humans
  • Immunity, Innate
  • Immunocompromised Host
  • Infant
  • Male
  • Middle Aged
  • Organ Transplantation*
  • Prospective Studies
  • Receptors, KIR / genetics*
  • Viremia / etiology
  • Viremia / genetics
  • Viremia / immunology
  • Virus Replication

Substances

  • Receptors, KIR