中国汉族人群中KIR分布规律及其在HLA相合亲缘造血干细胞移植中的作用

目的探讨杀伤细胞免疫球蛋白样受体（KIR）在中国汉族人群中的分布规律及其对人类白细胞抗原（HLA）相合亲缘移植预后的影响。方法采用PCR序列特异性引物（SSP）分型技术检测HLA及KIR基因型。检测了150例汉族人群中KIR的基因型分布、74例异基因造血干细胞移植供受者对KIR及HLA基因型,并对45例接受HLA相合亲缘移植、非去除T细胞异基因造血干细胞移植（allo—HSCT）的恶性血液病患者病例资料进行回顾性分析。结果KIR2DL1的基因分布频率为100％,KIR2DL2为20％,KIR2DL3为100％,KIR3DL1为95％。96％的供者携带与allo-HSCT关系密切的3组KIR受体。45例HLA相合亲缘供者中,36例患者KIR不合,占总人数的80％,其中35例患者KIR2DL1不合,1例KIR2DL2／2DL3不合,31例KIR3DL1不合。HLA相合亲缘供者移植患者中KIR2DL1不合组的急性移植物抗宿主细胞病（aGVHD）发生率（31％）明显低于KIR相合组（70％）,差异有统计学意义（P=0．029）。急性髓性白血病中KIR及KIR2DL1不合组的aGVHD发生率（18％）明显低于KIR相合组（75％）,差异有统计学意义（P=0．03）,淋巴系统疾病中差异无统计学意义。结论绝大多数中国北方汉族人群携带与allo—HSCT关系密切的3组KIR受体,HLA相合亲缘供者HSCT后供受者间KIR不合组aGVHD发生率明显下降。

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.