The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia.
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| Abstract |
Killer immunoglobulin-like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HLA-C, which subdivides into 2 groups based on the specificity of inhibitory KIRs. The ligands for activatory KIRs are unknown. Following hematopoietic stem cell transplantation (HSCT), recipient tissues may not express a ligand for KIRs present within the graft, and the combination of donor KIR and recipient HLA-C types could influence outcome. HLA and KIR genotypes were determined in 220 donor-recipient pairs from HLA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myeloid disease, overall survival was worse in patients homozygous for group 2 HLA-C (C2) than in patients who carried a group 1 HLA-C (C1) allele (P <.005). Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (P =.045). No effect was seen in patients with lymphoid disease. Thus, in HLA-matched sibling HSCT for myeloid leukemia, patients homozygous for C2 alleles receiving a graft from a donor carrying the KIR gene KIR2DS2 have a significantly reduced chance of survival.
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| Authors | Mark A Cook, Donald W Milligan, Christopher D Fegan, Philip J Darbyshire, Premini Mahendra, Charles F Craddock, Paul A H Moss, David C Briggs |
| Journal | Blood (Blood) Vol. 103 Issue 4 Pg. 1521-6 (Feb 15 2004) ISSN: 0006-4971 [Print] United States |
| PMID | 14504099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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