title: 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.
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Schmitter
authors.affiliation: 1] Infectious Diseases and Hospital Epidemiology, University Hospital, Basel, Switzerland [2] Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: H H
authors.initials: HH
authors.lastname: Hirsch
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Garzoni
authors.affiliation: Service of Infectious Diseases, University Hospital, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: van Delden
authors.affiliation: Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, St. Gallen, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Boggian
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zürich, Switzerland.
authors.forename: N J
authors.initials: NJ
authors.lastname: Mueller
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.affiliation: Transplant Immunology Unit, Division of Immunology and Allergy, University Hospital, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Villard
authors.affiliation: Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Meylan
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.affiliation: Immunobiology Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Hess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011446:Prospective Studies; D054340:Receptors, KIR / Q000235:genetics*; D014766:Viremia / Q000209:etiology / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D054340:Receptors, KIR