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

  • Gonzalez A Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
  • Schmitter K Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
  • Hirsch HH 1] Infectious Diseases and Hospital Epidemiology, University Hospital, Basel, Switzerland [2] Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Garzoni C Department of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland.
  • van Delden C Service of Infectious Diseases, University Hospital, Geneva, Switzerland.
  • Boggian K Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, St. Gallen, Switzerland.
  • Mueller NJ Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zürich, Switzerland.
  • Berger C Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich, Switzerland.
  • Villard J Transplant Immunology Unit, Division of Immunology and Allergy, University Hospital, Geneva, Switzerland.
  • Manuel O Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Meylan P Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Stern M Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
  • Hess C Immunobiology Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
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  • 2014-07-11
Published in:
  • Genes and immunity. - 2014
Adolescent
Adult
Aged
Child
Cytomegalovirus
Cytomegalovirus Infections
Female
Haplotypes
Humans
Immunity, Innate
Immunocompromised Host
Infant
Male
Middle Aged
Organ Transplantation
Prospective Studies
Receptors, KIR
Viremia
Virus Replication
English 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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  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/298314
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