[不同杀伤细胞免疫球蛋白样受体单倍型在单倍型相合造血干细胞移植中的作用]
[The role of different KIR haplotypes in haplo-identical hematopoietic stem cell transplantation].
作者信息
Bao Xiaojing, He Jun, Wang Miao, Yuan Xiaoni, Li Yang, Zhang Tengteng, Li Lingjie, Chen Luyao, Wu Depei
机构信息
Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou Institute of Blood and Marrow Transplantation, Suzhou 215006, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2016 Jan;37(1):20-5. doi: 10.3760/cma.j.issn.0253-2727.2016.01.004.
OBJECTIVE
To investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT).
METHOD
Killer cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents.
RESULTS
The family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045).
CONCLUSION
Overall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT.
目的
探讨不同免疫球蛋白样受体（KIR）单倍型在单倍型相合造血干细胞移植（HSCT）中的作用。
方法
采用聚合酶链反应-序列特异性引物（PCR-SSP）技术对156个无关家庭的468名个体进行杀伤细胞KIR基因分型。共使用来自父母的624个KIR单倍型进行单倍型分析。92例患者接受了来自父母一方的单倍型相合HSCT。
结果
家系研究显示一个A单倍型和至少20种独特的B单倍型的分离。单倍型A的频率为72.92%（455/624）。B组中最常见的单倍型是B1、B2和B3，频率分别为10.26%、5.77%和4.48%。与KIR基因匹配的供者（n = 17）相比，KIR基因不匹配的供者（n = 14）的移植物对AML/MDS患者单倍型相合HSCT后的生存有积极影响（总生存期：88.2%对42.9%，P = 0.015；无复发生存期：88.2%对35.7%，P = 0.007）。对ALL/NHL患者未观察到影响（总生存期：76.0%对75.0%，P = 0.727；无复发生存期：68.0%对65.0%，P = 0.866）。与其他Bx供者（n = 25）相比，来自AA（n = 52）和AB1/AB2供者（n = 15）的移植患者的生存率显著降低（总生存期：53.3%对96.0%，P = 0.017；无复发生存期：53.3%对92.0%，P = 0.019）。同时，AA组（n = 52）的复发风险比Bx组（n = 40）高得多（25.0%对5.0%，P = 0.009）。在AB1/AB2组中观察到较高的移植相关死亡率风险（P = 0.012）。此外，与携带Cen-A纯合子的供者相比，携带Cen-B的供者进行移植与生存率增加相关（总生存期：94.7%对68.5%，P = 0.036；无复发生存期：89.5%对64.4%，P = 0.045）。
结论
总体而言，KIR基因分型和单倍型分析有助于选择具有有利KIR基因移植物的最佳供者。对于AML/MDS患者，应优先选择KIR基因不匹配的供者。对于单倍型相合HSCT，强烈建议选择携带Cen-B的供者并避免选择KIR基因型为AA/AB1/AB2的供者。
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