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The impact of KIR receptor-HLA ligand interaction on the outcome of patients receiving HLA-matched sibling donor haematopoietic stem cell transplantation

The alloreactivity of NK cells is regulated by the interaction between killer immunoglobulin-like receptors (KIRs) of donor cells and human leukocyte antigen (HLA)-class I molecules on the target recipient cells. The main ligand for most inhibitory KIRs are HLA-Cw molecules and can be classified into two subgroups, C1 and C2. The HLA-KIR interactions has been shown to have a significant impact on the outcomes of haploidentical, unrelated donor and matched related donor allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to assess the impact of interaction between recipient HLA-Cw and donor KIR on HSCT outcome. KIR genotyping as well as HLA-C typing was performed by PCR-SSO method (Luminex). In the period from the year 2009 to 2011, 55 patients with hematological malignancies underwent HLA-matched, sibling donor HSCT at the University hospital center Zagreb. All 55 patients achieved platelet engraftment ; 36 of 55 patients were alive, and 19 patients died. The overall incidence of acute GVHD was 36% (20 patients) and that of chronic GvHD was 20% (11 patients). The impact of recipient HLA ligand subtypes on clinical outcome was evaluated. 28 (51%) patients were homozygous for either group C1 (18 patients) or group C2 (10 patients), and 27 (49%) were C1/C2 heterozygotes. Two years after HSCT, overall survival (OS) was not significantly different for C1 or C2 homozygotes than for C1/C2 heterozygotes. Based on the combination of HLA and KIR genotypes, OS two years after transplantation was higher in HLA-KIR matched patients than in mismatched cases (OS, 80% vs 55% ; P=0.026). For HLA-KIR-matched patients, there was a significantly lower incidence of GVHD (39% vs 73% ; P=0.025). Our data support the role of HLA-KIR interactions in clinical implications for optimising the selection of donors for allogeneic HSCT.

KIR receptors, HLA ligands, HSCT

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