The influence of donor killer immunoglobulin-like receptors and recipient HLA ligand matching in identical HLA-matched sibling adult haemopoietic stem cell transplantation

The objective of this study is to investigate the importance of Killer Immunoglobulin-like Receptor (KIR) receptor/ligand matching in Haemopoietic Stem Cell Transplantation (HSCT). HLA and KIR genes are located on different chromosomes so genetic identity is not guaranteed and means that the KIR gene and MHC-CI ligand may be mismatched even in HLA-identical related transplants. The study population included 177 consecutive HSC transplants for adult HLA-identical recipient and sibling donors performed between January 1998 and July 2005. The method of identifying the KIR genes was by molecular genotyping using Luminex LABType® PCR-SSO system. Data were analysed by correlation to established clinical endpoints of HSCT outcome. A score of possible donor receptor/recipient ligand interactions was calculated as documented by the Cleveland group (Sobecks,R. M. et al Bone Marrow Transplantation January 2008) and correlated to transplant outcome. Data for the presence of a particular receptor in the donor in combination with the presence of the appropriate ligand in the recipient was investigated and the influence the combination exerted on graft survival was analysed. Results: Analysis of the scores obtained for receptor/ligand matching showed no significant influence on transplant outcome. However analysis of matching of donor KIR receptor and recipient ligand pairs gave significant results for two KIR genes. Donor KIR2DL2 negative receptor and recipient C1 ligand negative transplant pairs had a significantly improved overall survival of 73% compared to donor 2DL2 positive receptor/ recipient C1 ligand positive pairs at 44%, p = 0.027. KIR2DS2 donor receptor negative/recipient C1 ligand positive had significantly improved survival of 67% compared to donor receptor positive/recipient ligand positive survival of 43%, p = 0.009. The ligand for KIR2DS3 is unknown so this analysis could not be made; KIR2DS3 is the subject of a further abstract. Conclusions: Engagement of donor inhibitory KIR2DL2 receptor and recipient C1 ligand inhibits GvL whereas engagement of donor activatory KIR2DS2 receptor and recipient C1 ligand enhances graft rejection. A balance between engagement of inhibitory and activatory KIR receptors and their ligands should be tailored by assessing the expression of KIR receptors on the donor NK cells prior to HSCT thus enabling manipulation of the GvL effect and improving the chances of increased graft survival.