非血缘关系HLA全相合造血干细胞移植中供者-受者NK细胞KIR的研究  

Study on the behavior of NK cell KIRs of donor/recipient pairs in HLA matched unrelated allo-HSCT

作　　者：鲍晓晶[1] 何军[1] 陈子兴[1] 吴德沛[1] 姚利[1] 袁晓妮[1] 岑建农[1] 邱桥成[1] 狄文英 张辉[2] 张健[2] 周晓华[2] 徐惠新[2] 

机构地区：[1]苏州大学附属第一医院,江苏省血液研究所,215006 [2]苏州市红十字中心血站

出　　处：《中华血液学杂志》2007年第8期510-513,共4页Chinese Journal of Hematology

基　　金：卫生部科研基金(wkj2006-2-023);江苏省卫生厅135开放项目(K0611)

摘　　要：目的研究自然杀伤细胞免疫球蛋白样受体(KIR)的生物学功能及供者抑制性 KIR 和受者 HLA 遗传背景在无关供者全相合造血干细胞移植(HSCT)中的作用。方法采用序列特异性引物聚合酶链反应(SSP-PCR)和序列特异性寡核苷酸探针聚合酶链反应(SSOP-PCR)的方法,对中国造血干细胞捐献者资料库中提供的51对 HLA 全相合供、受者进行 KIR 及 HLA 分型,患者中急性淋巴细胞白血病 ALL 18例,慢性粒细胞白血病(CML)15例,急性髓系白血病(AML)10例及其他患者8例。结果 51对供者-受者均存在 2DL1、2DL2/L3、2DLA、3DL2和3DL3,基因频率均为1,96.7%的个体表达 KIR3DL1。供-受者中21.57%KIR 完全相同;78.43%KIR 不完全相同,而 KIR 不相同又分为受者KIR 基因型包含供者 KIR 为25.49%,供者 KIR 基因型包含受者 KIR 为27.45%。74.62%的供者KIR2DL1无受者 C2配体,5.91%的供者 KIR2DL2/L3无受者 C1配体,19.74%的供者 KIR3DL1无受者 Bw4配体,54.91%的供者 KIR3D12无受者 A3、A11配体。结论 KIR 独特型和 HLA-Ⅰ类抗原是独立遗传的。供者 KIR2DL1和 KIR3DL2是主要引起 NK 细胞异源活性的受体,供、受者的 KIR/HLA 不匹配可能在全相合的无关供者异基因 HSCT 中起着十分重要的作用。KIR 受体-配体模型可以更好地提示 HSCT 的预后。bjective To study the biological function of killer cell immunoglobulin-like receptor （KIR） and the role of donor inhibitory KIR and recipient genetic background in HLA matched unrelated hematopoietic stem cell transplantation （HSCT）. Methods HLA genotype of 51 patients （ALL 18 cases, CML 15 cases, AML 10 cases and others 8 cases） and their respective matched unrelated donors from Database of China Marrow Registration was determined by polymerase chain reaction sequence oligonucleotide probes （PCR-SSOP） and sequence specific primers （PCR-SSP）. The KIR genotype was determined by PCR-SSP. Results All the patients and the donors expressed KIR2DL1, KIR2DL2/L3, KIR2DIA, KIR3DL2 and KIR3DL3. 96.7% individuals expressed KIR3DL1. Among them, 21.57% of KIR was completely identical, while 78.43% was not. Of the non-identical KIRs, 25.49% were the recipient＇s KIR genotype containing the donor＇s ones, and 27.45% was the donor＇ s containing the recipient＇s. 74.62% of donor＇s KIR 2DL1 lacked recipient＇ s C2 ligand, 5.91% of donor＇s KIR2DL2/L3 lacked recipient＇s C1 ligand, 19.74% of donor＇s KIR3DL1 lacked recipient＇s Bw4 ligand and 54.91% of donor＇s KIR3DL2 lacked recipient＇s A3, All ligand. Conclusion KIR genotype and HLA class Ⅰ antigen are inherited independently. KIR2DL1 and KIR3DL2 of donors may cause alloreactivity of NK cell. The mismatch of KIR/HLA in donor-recipient plays a very important role in matched unrelated allo-HSCT. The outcome of HSCT can be better predicted by the model of the presence of KIRs on the donor＇s NK cells and the absence of corresponding KIR ligand in the recipient＇s HLA.

关 键 词：杀伤细胞免疫球蛋白样受体 全相合无关供者 造血干细胞移植 杀伤细胞 天然 

分 类 号：R457[医药卫生—治疗学]