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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-02-0438.
Submitted February 10, 2003
Accepted September 4, 2003
The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling haematopoietic stem cell transplantation for myeloid leukaemia
Mark A Cook*, Donald W Milligan, Christopher D Fegan, Philip J Darbyshire, Premini Mahendra, Charles F Craddock, Paul A H Moss, and David C Briggs
Cancer Research UK [CRC] Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom; Department of Histocompatibility & Immunogenetics, National Blood Service, Birmingham, United Kingdom; Department of Haematology, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom
Department of Haematology, Birmingham Heartlands & Solihull NHS Trust, Birmingham, United Kingdom
Department of Haematology, Birmingham Childrens' Hospital, Birmingham, United Kingdom
* Corresponding author; email: markcook{at}blueyonder.co.uk.
Killer immunoglobulin-like receptors (KIRs) regulate cell activity of NK cells and some T-cells. The predominant ligand for inhibitory KIRs is HLA-C, which subdivides into two groups based on the specificity of inhibitory KIRs. The ligands for activatory KIRs are unknown. Following haematopoietic 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<0.005). Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (p=0.045). No effect was seen in patients with lymphoid disease. Thus, in HLA-matched sibling HSCT for myeloid leukaemia, 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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