title: Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients.
abstract: Killer cell immunoglobulin-like receptors (KIR) are highly polymorphic members of the immunoglobulin superfamily, which influence the response of natural killer cells and some T-lymphocyte subsets. Analysis of a cohort of previously human cytomegalovirus (HCMV)-negative patients, who developed primary HCMV infection following HCMV-positive renal transplant (n=76), revealed an increase in the frequency of KIR genes located on the telomeric region of B haplotypes (Tel B). The presence of Tel B in combination with the KIR ligand HLA-C2 was significantly more frequent in this subgroup. These genetic factors were associated with resistance to HCMV infection in a second cohort (n=65), where the Tel B genes KIR2DL5, -2DS1, 2DS5 and -3DS1 were all significantly associated with high viral loads. Furthermore, the KIR haplotype Tel A when in combination with the KIR ligand HLA-C1 was significantly protective against the development of severe infection. Our results suggest that KIR are a significant factor in the control of primary HCMV infection, and that determination of KIR gene repertoire may help in detection of renal transplant patients who were most at risk.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Jones
authors.affiliation: Tissue Typing Laboratory, Cambridge University Hospitals, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Peacock
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Traherne
authors.affiliation: Centre for Infection and Immunity, St. George's Hospital, University of London, London, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Allen
authors.affiliation: Transplant Immunology Laboratory, Churchill Hospital, Oxford, UK.
authors.forename: M C N M
authors.initials: MC
authors.lastname: Barnardo
authors.affiliation: Oxford Transplant Centre, Churchill Hospital, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Friend
authors.affiliation: Tissue Typing Laboratory, Cambridge University Hospitals, Cambridge, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Taylor
authors.affiliation: Transplant Immunology Laboratory, Churchill Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Fuggle
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Trowsdale
authors.affiliation: Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: N T
authors.initials: NT
authors.lastname: Young
mesh_terms: D015331:Cohort Studies; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000235:genetics* / Q000821:virology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D054884:Host-Pathogen Interactions; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D054340:Receptors, KIR / Q000235:genetics*; D054346:Receptors, KIR2DL5 / Q000235:genetics; D054349:Receptors, KIR3DS1 / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D016615:Telomere / Q000235:genetics; D019562:Viral Load
chemical_list: D015236:HLA-C Antigens; C496212:KIR2DS1 protein, human; C531595:KIR2DS5 protein, human; D054340:Receptors, KIR; D054346:Receptors, KIR2DL5; D054349:Receptors, KIR3DS1