激活性KIR受体在HLA全相合无关供体异基因造血干细胞移植中的作用  

Impact of activating KIR on outcome of matched unrelated allo-hematopoietic stem cell transplantation

作　　者：何军[1] 鲍晓晶[1] 孙爱宁[1] 陈子兴[1] 袁晓妮[1] 邱桥成[1] 岑建农[1] 姚利[1] 吴德沛[1] 阮长耿[1] 

机构地区：[1]苏州大学附属第一医院,苏州215006

出　　处：《中华细胞与干细胞移植（电子版）》2009年第1期27-30,共4页

基　　金：卫生部科研基金资助项目（wkj2006-2-023）; 江苏省六大高峰人才（07-B-021）; 江苏省高校自然科学基金（07kj320106）; 苏州市中外国际合作项目（SWH0716）; 苏州市基础设施项目（SZS0702）

摘　　要：目的对不同激活性KIR受体（aKIR）在HLA全相合无关供体异基因造血干细胞移植中的作用进行研究。方法采用序列特异性引物聚合酶链反应（PCR-SSP）和基因测序（SBT）方法,对中国造血干细胞捐献者资料库中提供的74对HLA全相合供受者进行KIR及HLA高分辨分型,其中38例进行了异基因造血干细胞移植,接受移植的患者FAB分型为ALL18例、CML8例、AML12例,移植后的患者随访到2008年12月。结果在74对供受者中100﹪有KIR2DS4基因,64.87﹪有KIR2DS1基因,60.81﹪有KIR3DS1基因,45.95﹪有KIR2DS5基因,44.6﹪有KIR2DS2基因,35.14﹪有KIR2DS3基因。在AML和CML分型的移植中供者有激活性KIR2DS1、KIR2DS3和KIR3DS1基因高表达;而在ALL分型的移植中低表达。在表达KIR2DS4的供受者中,其中51.4﹪仅表达2DS4＊001/002亚型,23.6﹪仅表达2DS4＊003-007亚型,25.0﹪为两种亚型同时表达。供受者仅有2DS4＊001/002亚型的病例均在移植后死亡;供者具有2DS4＊003-007亚型的病例1年无病生存率为83.3﹪。当供者aKIR基因数目≥3个时,ALL患者的1年无病生存率为87.50﹪;当供者aKIR基因数目〈3个时,AML/CML患者1年无病生存率为83.33﹪。结论在无关供体异基因造血干细胞移植中,KIR单体型A、激活性KIR受体基因亚型和数目的差异表达,对降低GvHD的发生和移植的预后起关键作用。0bjective To explore the impact of different activating KIRs in HLA matched unrelated allo-hematopoietic stem cell transplantation.Methods The HLA/KIR genotype of 74 patients and their recipient matched unrelated donors from database of CMDP were determined by polymerase chain reaction sequence oligonucleotide probes（PCR-SSOP）and sequence specific primers（PCR-SSP）.38 patients received unrelated allo-HSCT.Among them,18 were ALL,8 were CML and 12 were AML by FAB typing.All patients were followed up until December 2008. Results The frequencies of KIR2DS4,KIR2DS1,KIR3DS1,KIR2DS5,KIR2DS2 and KIR2DS3 were 100.0﹪,64.87﹪,60.81﹪,45.95﹪,44.6﹪,and 35.14﹪respectively in 74 pairs of donor-recipient.Frequencies of activating KIR2DS1,KIR 2DS3 and KIR 3DS1 genotypes were much higher in donors of AML and CML groups,but low in ALL group.The frequencies of KIR2DS4＊001/002 and 2DS4＊003-007 homozygotes were 51.4﹪and 23.6﹪respectively,while the frequency for 2DS4＊001/002 and 2DS4＊003-007 heterozygote was 25.0﹪.The mortality rate was 100﹪when the patient and donor had the same KIR2DS4＊001-002.The disease-free survival（DFS） of one year was 83.3﹪when the donor had 2DS4＊003-007.The DFS of one year was 87.50﹪when the donors have three or more aKIR in ALL group.But for AML/CML,it was 83.33﹪if the donor had one or two aKIR.Conclusion The KIR genotyping in haplotype A and the differential expression of the number and subtype in aKIR may be related to the reduce occurrence of aGVHD and better clinical outcome in unrelated Allo-HSCT.

关 键 词：造血干细胞移植 活化型KIR受体 抑制型KIR受体 预后 

分 类 号：R457.7[医药卫生—治疗学]