title: KIR-ligand mismatches are associated with reduced long-term graft survival in HLA-compatible kidney transplantation.
abstract: Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system with the ability to detect HLA class I disparities via killer-cell immunoglobulin-like receptors (KIR). To test whether such KIR-ligand mismatches contribute to the rejection of human solid allografts, we did a retrospective cohort study of 397 HLA-DR-compatible kidney transplantations and determined the KIR and HLA genotypes of recipients and the HLA genotypes of donors. In transplantations compatible for HLA-A, HLA-B and HLA-DR (n = 137), in which a role for T cells and HLA antibodies in rejection was minimized, KIR-ligand mismatches were associated with an approximately 25% reduction in 10-year death-censored graft survival (p = 0.043). This effect was comparable to the effect of classical HLA-A and HLA-B incompatibility, and in HLA-A,-B-incompatible transplantations (n = 260) no significant additional effect of KIR-ligand mismatches was observed. Multivariate Cox regression analysis confirmed the effect of KIR-ligand mismatching as an independent risk factor in HLA-A,-B,-DR-compatible transplantations (hazard ratio 2.29, range 1.03-5.10, p = 0.043). This finding constitutes the first indication that alloreactive NK cells may thwart the success of HLA-compatible kidney transplantations, and suggests that suppression of NK-cell activity can improve the survival of such kidney grafts.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. J.van_Bergen@lumc.nl
authors.forename: J
authors.initials: J
authors.lastname: van Bergen
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: G W
authors.initials: GW
authors.lastname: Haasnoot
authors.forename: J I
authors.initials: JI
authors.lastname: Roodnat
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.forename: F
authors.initials: F
authors.lastname: Koning
authors.forename: I I N
authors.initials: II
authors.lastname: Doxiadis
mesh_terms: D005260:Female; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation; D008024:Ligands; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D008024:Ligands; D054340:Receptors, KIR