P202 KIR matching and KIR haplotype frequencies in hematopoietic stem cell transplant (HSCT) patients and HLA matched related donors

Abstract

Aim Studies have shown that natural killer cells play an important role in mediating a graft-versus-leukemia effect through the interaction of NK cell receptors that can recognize ligands on their target cells. Interactions between the killer-cell immunoglobulin-like receptors (KIR) and their HLA ligands could influence outcomes in several clinical conditions including infections, autoimmunity and cancer. Patients with certain leukemia (e.g., AML) could benefit from hematopoietic stem cell transplant (HSCT) with NK-alloreactive donors resulting in significantly lower relapse rate. The aim of the study was to investigate first the KIR matching and KIR haplotype frequencies among HSCT patients and their HLA matched donors in order to further study the NK impact on transplant outcomes. Methods 149 pairs of HSC transplanted patients and their HLA matched related donors (7 with 1 DP mismatch) were included in the study. Patients and donors were high resolution typed at all HLA class I and class II loci. KIR genotyping were performed using fluorescently labelled beads conjugated to oligonucleotide probes (reverse SSO) and detected in a Luminex platform. KIR haplotype A or B were assigned per KIR genes content. Results Out of the 149 HLA matched pairs, 50 (33.6%) were also KIR matched and 99 (66.4%) KIR not matched for at least one KIR gene. KIR haplotypes were found A/A 31.5%, A/B 60.4%, and B/B 8.1% in patients; and KIR A/A 38.9%, A/B 57.1%, and B/B 4.0% in donors. Conclusions Because HLA genes and KIR genes are encoded on different chromosomes (6 and 19, respectively), one would expect KIR mismatch between HLA full matched family members. KIR mismatching could be beneficial to transplant patients from the NK alloreactivity of the donor. We have observed about one third HLA and KIR matched pairs. Further study on transplant outcomes between those HLA/KIR matched and HLA matched/KIR not matched groups would be warranted aiming for better donor selection to improve outcome. Better outcomes have been shown from donor with two or more KIR B motifs especially centromeric ones. Further outcome study from these transplants pairs would provide important information and understanding of the impact of these KIR haplotypes especially those donors with KIR A/A which could be disadvantageous to the patient for a better outcome.