title: Donor-recipient combinations of group A and B KIR haplotypes and HLA class I ligand affect the outcome of HLA-matched, sibling donor hematopoietic cell transplantation.
abstract: The influence of donor and recipient killer immunoglobulin-like receptor (KIR) genotype on the outcome of hematopoietic cell transplantation between human leukocyte antigen (HLA)-matched siblings was investigated. Transplants were divided into four groups according to the combination of group A and B KIR haplotypes in the transplant donor and recipient. Overall survival of myeloid patients varied with KIR genotype combination. Best survival was associated with the donor lacking and the recipient having group B KIR haplotypes; poorest survival was associated with the donor having and the recipient lacking group B KIR haplotypes. The latter combination was also associated with increased relapse and acute graft-versus-host disease (GVHD). However, its detrimental effects were seen only for transplants where the recipient and donor were homozygous for the C1 KIR ligand and therefore lacked the C2 ligand. Presence of the Bw4 ligand was also associated with increased acute GVHD. In contrast presence of both KIR3DL1 and its cognate Bw4 ligand was associated with decreased nonrelapse mortality. Analysis of the KIR genes individually revealed KIR2DS3 as a protective factor for chronic GVHD. The results suggest how simple assessments of KIR genotype might inform the selection of donors for hematopoietic cell transplantation.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Karina L
authors.initials: KL
authors.lastname: McQueen
authors.forename: Kristel M
authors.initials: KM
authors.lastname: Dorighi
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: Ruby
authors.initials: R
authors.lastname: Wong
authors.forename: Bharati
authors.initials: B
authors.lastname: Sanjanwala
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005787:Gene Frequency; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing / Q000706:statistics & numerical data; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D012307:Risk Factors; D035781:Siblings; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1