KIR/HLA ligand incompatibility in kidney transplantation

The polymorphic family of killer-cell immunoglobulin-like receptors (KIRs) consists of activating and inhibitory receptors expressed by natural killer (NK) cells and effector T cells that recognize human leukocyte antigen (HLA) class I ligands. It has been suggested that KIR/HLA incompatibility exerts beneficial effects in hematopoietic stem cell transplantation.

To elucidate whether certain receptor-ligand combinations between recipient KIR and donor HLA antigens lead to enhanced alloreactivity of NK cells associated with acute rejection (aRx) after kidney transplantation, we analyzed the entirety of matches/mismatches between KIR genes and known HLA ligands for aRx patients (n=105) compared to patients with stable renal function (n=119).

Whereas HLA-C ligand incompatibility between donor and recipient has no influence on aRx, grafts derived from donors homozygous for HLA-C group 2 alleles seem to demonstrate a better outcome (P=0.052). Additionally, a higher number of inhibitory receptors in the recipient's genotype (P=0.042), a significant higher number of matches for the receptors KIR2DL2/DS2 (P=0.004), as well as a higher number of mismatches for KIR2DL3 (P=0.014) could be observed for patients with stable renal function.

Our data illustrate that certain KIR/HLA class I ligand combinations between donor and recipient might influence graft short-term outcome after renal transplantation.