Prognostic role of KIR genes and HLA-C after hematopoietic stem cell transplantation in a patient cohort with acute myeloid leukemia from a consanguineous community

NK cell activity is tuned by a balance of activating and inhibitory signals transmitted via their respective receptors, including killer immunoglobulin-like receptors (KIRs). The impact of NK cells on graft-versus-leukemia following hematopoietic stem cell transplantation (HSCT) is well established. These effects sometimes lead to GvHD. The link between KIR/HLA interaction and GvHD remains unclear. Herein, we studied the impact of the KIR/HLA interaction on HSCT outcomes in a longitudinal follow-up study of a highly consanguineous HLA-matched related cohort. Peripheral blood DNA was collected from HSCT donor–recipient pairs ( n = 87), including 41 AML pairs. KIR and HLA were genotyped and significant results were only measured when matching KIR (donor) with HLA (recipients). GvHD was observed in 47% of patients. KIR2DL1_C2 and 2DS2_C1 ( P = 0.02 and 0.04, respectively) matching was associated with an increased incidence of acute GvHD in AML donor–recipient pairs. The rate of chronic GvHD also rose in AML patients who were matched for KIR2DS1_C2 ( P = 0.004) and had either KIR2DL2 or KIR2DS2 ( P = 0.03). In conclusion, matching of KIR2DL1, 2DS1 , and 2DS2 in donors with their HLA-C ligands in recipients is associated with increased GvHD, and holds potential for selection of HSCT donors.