Distribution of immunoglobulin like receptor gene in Han population in China and the impact thereof on the HLA-identical sibling hematopoietic stem cell transplantation

Abstract

To investigate the distribution of killer immunoglobulin like receptor (KIR) gene in the Han population in north China and the impact of donor KIR and patient HLA genotypes on the outcome of HLA-identical sibling hematopoietic stem cell transplantation patients with hematological malignancy. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to detect the KIR distribution of 150 healthy people and the KIR genotype of donor and HLA genotype of allogeneic stem cell transplantation recipients of 74 donor-recipient pairs, and a retrospective study was carried out to analyze the outcomes of 45 patients with various hematological malignancies who received non T-cell-depleted transplant from HLA-identical sibling donors, all the subjects being of Han nationality in north China. The gene frequencies of KIR2DL1, KIR2DL2, KIR2DL3, and KIR3DL1 were 100%, 20%, 100%, and 95% respectively. 96% of the allogeneic donors carried one of the 3 class I ligands of inhibitory KIR. 36 of the 45 (80%) donor-recipient HLA-identical sibling transplant pairs lacked recipient HLA ligand for donor KIR, among which 35 lacked recipient HLA ligand for donor KIR2DL1, 1 pair lacked that for KIR2DL2/2DL3, and 31 pairs lacked that for KIR3DL1. Cumulative incidence analysis of graft versus host disease (GVHD) in the patients undergoing HLA-identical sibling hematopoietic stem cell transplantation demonstrated that the incidence of severe acute GVHD (aGVHD) in the patients lacking HLA ligand for donor-inhibitory KIR2DL1 was 31%, significantly lower than that of the patients with HLA ligand for donor-inhibitory KIR2DL1 (70%, P = 0.029), and the incidence of severe aGVHD in the acute myeloid leukemia patients lacking HLA ligand for donor-inhibitory KIR and KIR2DL1 was 18%, significantly lower than that of the KIR compatible patients (75%, P = 0.03). Almost all Chinese of Han nationality in north China carry having one of the 3 known class I ligands of inhibitory KIR. KIR and KIR2DL1 mismatch is associated with lower aGVHD after HLA-identical sibling hematopoietic stem cell transplantation.