KIR-Ligand Mismatches Are Associated With Reduced Long-Term Graft Survival in HLA-Compatible Kidney Transplantation

J van Bergen, A Thompson, GW Haasnoot, J.I. Roodnat, JW de Fijter, FHJ Claas, F Koning, IIN Doxiadis

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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.
Original languageUndefined/Unknown
Pages (from-to)1959-1964
Number of pages6
JournalAmerican Journal of Transplantation
Volume11
Issue number9
DOIs
Publication statusPublished - 2011

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