异基因造血干细胞移植中非血缘供者KIR2DL1、KIR3DL1免疫重建规律的研究  

Immune reconstruct regularity profile of KIR2DL1 and KIR3DL1 in unrelated-donor allogeneic hematopoietic stem cell transplantation

作　　者：胡星[1] 何军[1] 张环环[1] 鲍晓晶[1] 王苗[1] 张静[1] 岑建农[1] 吴小津[1] 杨小静[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所、临床检测中心,215006

出　　处：《中华血液学杂志》2017年第8期667-672,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81671549、81600142、81072435）;江苏省医学创新团队与领军人才（CXTDB2017009）;江苏省临床医学科技专项（BL2014038）

摘　　要：目的在非血缘供者为杀伤细胞免疫球蛋白样受体（ⅪR）．AA基因型的异基因造血干细胞移植（allo．HSCT）中研究KIR2DLl、KIR3DLl的免疫重建规律。方法采用序列特异性引物PCR、流式细胞术和实时荧光定量PCR法，对75对供受者进行KIR基因分型，确定供者均为KIR．AA基因型，并动态检测移植当天及移植后不同时间澎植后0．5个月～〈1．5个月（1个月）、移植后1．5个月～〈2．5个月（2个月）、移植后2．5个月～〈3．5个月（3个月）、移植后3．5个月～〈6．5个月（3-6个月）、移植后6．5个月～〈9．5个月（6-9个月）、移植后9．5个月〈12．5个月（9～12个月）]KIR2DLl、KIR3DLl膜蛋白和mRNA的表达水平。结果KIR2DL膜蛋白中位表达水平：非血缘供者移植当天为21．60％，受者在1、2、3、3-6个月时表达水平分别为7．40％、12．00％、16．92％、17．64％；KIR2DLl的mRNA中位表达水平：非血缘供者移植当天为265．14／10。ABL拷贝数，受者移植后1、2、3、3-6、6-9、9-12个月时表达水平分别为332．17、438．31、723．25、414．17、187．60及234．67／10。ABL拷贝数。KIR2DLl的mRNA和膜蛋白表达水平在移植后各个时间点均逐渐升高，且在3个月后达到最高，但mRNA表达水平升高早于膜蛋白。（2）KIR3DLl膜蛋白中位表达水平：非血缘供者移植当天为18．56％，受者在移植后1、2、3、3-6个月时表达水平分别为23．83％、22．57％、23．02％、21．60％；KIR3DLlmRNA中位表达水平：非血缘供者移植当天为572．29／10。ABL拷贝数，受者移植后1、2、3、3-6、6-9、9-12个月时表达水平分别为1233．74、1140．42、876．73、1057．07、739．02、514．43／10。ABL拷贝数。KIR3DLl的mRNA和膜蛋白在移植后1个月的表达水平均已超过了非血缘供者，并在移植后各个时间点均稳定高表达，且mRNA与膜蛋白表达水平同步升高。结论KIR2DLl和KIR3DLl�Objective To investigate the immune reconstruct regularity profile of K1R2DL1 and KIR3DL1 in unrelated-donor allogeneic hematopoietic stem cell transplantation （allo-HSCT） with KIR- AA genotype. Method 75 donor-recipient pairs were performed by KIR genotying using PCR-SSP, and all donors were identified with KIR-AA genotype. Dynamic detections （including unrelated-donor on the day of transplantation and the recipient each month post allo-HSCT） of the expression of KIR2DL1/3DL1 on NK cell and mRNA level were performed in 291 cases using flow cytometry （FCM） and real-time fluorescent quantitation PCR （RT-qPCR）. Result （1）The median expression of KIR2DLI in unrelated- donor on transplant＇ s day was 21.60%, the median expression of KIR2DL 1 in recipient 1 M, 2M, 3M and 3- 6M after transplantation were 7.40%, 12.00%, 16.92%, 17.64% respectively. The median expression of KIR2DL1 in unrelated-donor on transplant＇ s day was 265.14 copies/10 000abl copies, the medianexpression of KIR2DL1 in recipient 1M, 2M, 3M, 3-6M, 6-9M, 9-12M after transplantation were 332.17, 438.31,723.25,414.17, 180.76 and 234.67 copies/10 000abl copies respectively. The median expression of KIR2DL1 on NK cells and mRNA level gradually increased at all time points after transplantation, and reached the highest expression at 3 months after transplantation. But mRNA expression levels increased earlier than NK cell membrane proteins. @The median expression of KIR3DL1 in unrelated-donors on transplant＇ s day was 18.56%, the median expression of KIR3DL1 in recipient 1M, 2M, 3M, 3-6M after transplantation were 23.83%, 22.57%, 23.02%, 21.60% respectively. The median expression of KIR3DL1 in unrelated-donor on transplant＇ s day was 572.29 copies/10 000abl copies, the median expression of KIR3DL1 in recipient 1M, 2M, 3M, 3-6M, 6-9M, 9-12M after transplantation were 1 233.74, 1 140.42, 876.73, 1 057.07, 739.02 and 514.43 copies/10 000abl copies respectively. The median expression of KIR3DL1 on NK cells and mRNA level were higher t

关 键 词：受体 KIR 造血干细胞移植 杀伤细胞 天然 免疫重建 

分 类 号：R457.7[医药卫生—治疗学]