title: Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation.
abstract: Recognition of HLA-C molecules by killer cell immunoglobulin-like receptors (KIRs) is an important mechanism in the regulation of natural killer (NK) cell activity. Eradication of residual leukaemic cells by alloreactive donor NK cells after haematopoietic stem cell transplantation (HSCT) fulfils a crucial role in the control of relapse. This retrospective study evaluates 83 patients and their related donors. All individuals were typed at low-resolution level to determine their HLA repertoire. KIR genotyping data were obtained by the use of sequence-specific oligonucleotide (SSO) analysis. All data were combined with patient and donor characteristics and post-transplant clinical data. A higher overall survival was seen when KIR2DS1 in the donor was mismatched with the HLA-C group 2 ligand in the patient (p=0.03). The number of activating KIRs either in the patient or in the donor was significantly correlated with the occurrence of relapse (p=0.003 and p=0.02, respectively). In addition, the presence of KIR2DS5 in the patient alone or in both the patient and donor was significantly correlated with the occurrence of relapse (p=0.004 and p=0.005, respectively). In conclusion, significant correlations were found for activating KIRs with overall survival and relapse.
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schellekens
authors.forename: Erik H
authors.initials: EH
authors.lastname: Rozemuller
authors.forename: Eefke J
authors.initials: EJ
authors.lastname: Petersen
authors.forename: Jan G
authors.initials: JG
authors.lastname: van den Tweel
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR