Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants

D. De Santis, A. Bishara, Campbell Witt, A. Nagler, C. Brautbar, S. Slavin, Frank Christiansen

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62 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)519-528
JournalTissue Antigens
Volume65
Issue number6
DOIs
Publication statusPublished - 2005

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