title: Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants.
abstract: Matching of donor and recipient for the class I human leukocyte antigen-C (HLA-C)-encoded natural killer (NK) epitopes has been reported to influence stem-cell (SC) graft outcome, but a consistent picture has not yet emerged. We have analyzed transplant outcome in 104 unrelated SC grafts in relation to NK epitope (C1 and C2) matching and donor killer cell immunoglobulin-like receptor (KIR) genotype. NK epitope mismatching in the rejection direction was strongly associated with an increased probability of rejection subsequent to engraftment. The prevalence of grades III-IV acute graft-vs-host disease (GVHD) was significantly higher and occurred significantly earlier when there was NK epitope mismatching in the GVH direction. Higher transplant-related mortality and lower disease-free survival rates were associated with epitope mismatching regardless of the mismatch direction. A greater number of KIR receptors, both activating and inhibitory, in the donor protected against grades III-IV GVHD and improved survival.
authors.affiliation: Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia.
authors.forename: D
authors.initials: D
authors.lastname: De Santis
authors.forename: A
authors.initials: A
authors.lastname: Bishara
authors.forename: C S
authors.initials: CS
authors.lastname: Witt
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.forename: C
authors.initials: C
authors.lastname: Brautbar
authors.forename: S
authors.initials: S
authors.lastname: Slavin
authors.forename: F T
authors.initials: FT
authors.lastname: Christiansen
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D000939:Epitopes / Q000737:chemistry*; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D005838:Genotype; D006086:Graft vs Host Disease; D015236:HLA-C Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology; D054340:Receptors, KIR; D012008:Recurrence; D033581:Stem Cell Transplantation; D013997:Time Factors; D019172:Transplantation Conditioning; D014181:Transplantation Immunology; D016896:Treatment Outcome
chemical_list: D000939:Epitopes; D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR