TY - JOUR
T1 - The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling haematopoietic stem cell transplantation for myeloid leukaemia
AU - Cook, Mark
AU - Milligan, Donald
AU - Fegan, Christopher
AU - Darbyshire, Philip
AU - Mahendra, Premini
AU - Craddock, Charles
AU - Moss, Paul
AU - Briggs, David
PY - 2003/10/23
Y1 - 2003/10/23
N2 - Killer immunoglobulin-like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HILA-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 HILA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myelold 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.
AB - Killer immunoglobulin-like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HILA-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 HILA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myelold 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.
U2 - 10.1182/blood-2003-02-0438
DO - 10.1182/blood-2003-02-0438
M3 - Article
C2 - 14504099
SN - 1528-0020
VL - 103
SP - 1521
EP - 1526
JO - Blood
JF - Blood
IS - 4
ER -