Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation.
Reactivation of cytomegalovirus (CMV) is a common complication following allogeneic stem cell transplantation. Genetic determinants in the host and donor that may influence the rate of reactivation are currently unknown. Viral replication is controlled by T cells and natural killer (NK) cells and these share expression of killer immunoglobulin-like receptors (KIRs). We analyzed whether activatory KIRs carried by the donor influenced the subsequent rate of CMV reactivation in the patient. In transplantations involving siblings where both donor and recipient were CMV seropositive, donors with more than one activating KIR gene were associated with a 65% reduction in CMV reactivation. Multivariate analysis confirmed a significantly reduced risk of CMV reactivation in sibling transplantations where the donor had more than one activating KIR. Reduced-intensity transplantation and graft-versus-host disease grade 2 or higher were associated with an increased risk of CMV reactivation. This observation indicates that activating KIRs play an important role in the cellular control of CMV reactivation.
Cook
Mark
M
Department of Haematology, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, United Kingdom. markcook@uhb.nhs.uk
Briggs
David
D
Craddock
Charles
C
Mahendra
Premini
P
Milligan
Donald
D
Fegan
Christopher
C
Darbyshire
Philip
P
Lawson
Sarah
S
Boxall
Elizabeth
E
Moss
Paul
P
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D035781:Siblings; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D014775:Virus Activation / Q000276:immunology
D017874:Immediate-Early Proteins; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins