Next generation sequencing of the Killer Immunoglobulin-like Receptor (KIR) gene cluster in the context of haemopoietic progenitor cell transplantation: Considering KIR genomics and proteomics within donor selection algorithms

Abstract

Killer Immunoglobulin-like Receptors (KIR) are receptors important in the cytotoxic action of natural killer (NK) cells. These receptors are known to be a predictor of haemopoietic progenitor stem cell transplantation (HPCT) outcomes. Current models in routine use for the selection of donors for HPCT assess the presence or absence of the genes encoding these receptors. KIR genes are also highly polymorphic, with allelic polymorphisms influencing the surface density of the receptor on NK cells, the binding affinity with their cognate ligand, and the signalling strength of the receptor. With the advent of next generation sequencing, it is now viable for clinical laboratories to efficiently sequence KIR genes. A limited number of studies have identified the influence of the allelic polymorphism of some KIR genes influence HPCT outcomes, but this area remains relatively unexplored. This study aims to explore the KIR allelic polymorphism frequencies within the local Manchester transplant cohort and the influence of KIR allelic polymorphism on HPCT outcomes in a single centre cohort of adult AML patients, with an aim to establish a novel algorithm for the selection of the optimal HPCT donor.

Outputs

Wright, Paul (2020) Killer-cell immunoglobulin-like receptor assessmentalgorithms in haemopoietic progenitor cell transplantation:current perspectives and future opportunities. HLA. 95: 435-448. https://onlinelibrary.wiley.com/doi/10.1111/tan.13817