title: The diversity of KIR gene in Chinese Northern Han population and the impact of donor KIR and patient HLA genotypes on outcome following HLA-identical sibling allogeneic hematopoietic stem cell transplantation for hematological malignancy in Chinese people.
abstract: Killer cell immunoglobulin-like receptors (KIRs) are members of a group of molecules that specifically recognize HLA class I ligands and are found on subsets of human lymphopoetic cells. The number of KIR loci can vary between individuals, resulting in a heterogeneous array of possible KIR genes. The range of observed profiles has been explained by the occurrence of two haplotype families termed A and B, which can be distinguished on the basis of certain KIR sequences. Immunogenetic analysis of different ethnic populations shows significant differences in terms of the distribution for group A and group B haplotypes. Recently, attention has been focused on the role of killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction between donor and recipient in allogeneic hematopoietic stem-cell transplantation (ASCT). The goal of this study was to study the frequency of specific KIR genes in Chinese Northern Han population and evaluate the role of KIR-ligand mismatch in Chinese HLA-identical sibling hematopoietic stem cell transplantation patients with hematological malignancy. Here genomic DNA from 150 Northern Chinese Han individuals was typed for the presence or absence of KIR genes. Seventy-four allogeneic stem cell transplantation donor/recipient pairs were typed for HLA-A, B, C and KIR. Sixteen KIR genes were observed in the population, and framework genes 3DL3, 3DP1, 2DL4, and 3DL2 were present in all individuals. Twenty-two different genotypes were found. Group A haplotypes outnumbered group B haplotypes in frequency by approximately 3:1, with individuals having two group A haplotypes accounting for 51.9% (78/150). We observed that 57 out of 74 (77.3%) donor-recipient pairs could be characterized by lack of recipient HLA ligand for donor KIR. We observed that 36 out of 45 (80%) donor-recipient HLA-identical sibling transplant pairs could be characterized by lack of recipient HLA ligand for donor KIR. Cumulative incidence analysis of aGVHD in patients undergoing HLA-identical sibling hematopoietic stem cell transplantation in this study demonstrated a decreased incidence of severe aGVHD in patients lacking HLA ligand for donor-inhibitory KIR2DL1 (31.4 vs. 70%, P = 0.029). And also in AML (acute myeloid leukemia) patients lacking HLA ligand for donor-inhibitory KIR and KIR2DL1 (17.6 vs. 75%, P = 0.03). Our data demonstrated that the Chinese Han population is distinct in KIR gene frequencies and putative KIR haplotypes in comparison to some other populations. Almost all allogeneic donors could be characterized as having an inhibitory KIR for each of the three known class I ligands. KIR and KIR2DL1 mismatch is associated with lower aGVHD in Chinese after HLA-identical sibling hematopoietic stem cell transplantation.
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Dou
authors.affiliation: PLA Transplant Center, PLA General Hospital of China, Beijing, 100091, China.
authors.forename: De Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Jun Hua
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Jing Fen
authors.initials: JF
authors.lastname: Sun
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Hai Jie
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Chun Ji
authors.initials: CJ
authors.lastname: Gao
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Hematology, PLA General Hospital of China, 28 Fuxing Road, Beijing, 100853, China. dwanming@hotmail.com.
authors.forename: Wan Ming
authors.initials: WM
authors.lastname: Da
mesh_terms: D044466:Asian People / Q000235:genetics*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008024:Ligands; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D035781:Siblings; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D008024:Ligands; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins