杀伤细胞免疫球蛋白样受体及其配体对亲缘供者造血干细胞移植预后的影响

Effects of Killer Immunoglobulin-like Receptor and Human Leukocyte Antigen ClassⅠ Ligand on the Prognosis of Related Donor Hematopoitic Stem Cell Transplantation

目的检测杀伤细胞免疫球蛋白样受体(KIR)及其配体-人类白细胞抗原Ⅰ(HLAⅠ-)基因分布频率,评估两者的相互作用对亲缘供者造血干细胞移植(HSCT)预后的影响。方法采用序列特异性引物聚合酶链反应(PCR-SSP)检测87对亲缘供者HSCT供受者(半倍体相合40对,同胞完全相合47对)的HLA-Cw及供者KIR基因型。结果87例正常供者均携带抑制型KIR2DL1、2DL2/L3、2DL4、3DL2和3DL3,基因频率为1;其次是3DL1,基因频率为96.6%;激活型KIR基因频率不一。87例受者的C1表达率为97.7%,而C2、Bw4、HLA-A3/A11的表达率不一。半倍体相合HSCT中KIR-HLA配体不合34例,相合6例;HLA-HLA配体相合31例,不合9例。同胞完全相合HSCT中KIR-HLA配体不合42例,相合5例。KIR-HLA配体不合组移植后2年无病生存率为(71.5±6.5)%,明显高于相合组的(50.0±10.7)%(P<0.05)。结论激活型KIR的基因频率明显低于抑制型KIR基因频率,抑制型KIR2DL1、3DL1、3DL2可能对NK细胞同种反应性起主要作用。KIR-HLA配体不合亲缘供者HSCT患者的无病生存率明显高于KIR-HLA配体相合者。

Objective To study the genotype distribution and the effects of killer immunoglobulin- like receptors （KIR） and human leukocyte antigen （HLA） class I ligand on related donor hematopoietic stem cell transplantation （HSCT）. Metholds The genotypes of donor/recipient HLA-Cw and donor K/R were determined by polymerase chain reaction-sequence specific primer （ PCR-SSP ） in 87 cases of related donor HSCT （40 cases were haploidentical HSCT, and the remaining 47 cases were HLA-identital sibling HSCT）. Results All the donors possessed KIR2DL1, 2DL2/L3, 2DL4, 3DL2, and 3DL3, and 96. 6% of donors possessed 3DLI. The rate of activating KIRs varied. 97.7% of the recipients expressed C1, while the rates of C2, Bw4, and HLA-A3/All were different. In haploidentical HSCT, KIR-HLA-mismatched group included 34 cases and the matched group included 6 cases. HLA-HLA-mismatched group included 31 cases and the matched group included 9 cases. In matched sibling donor HSCT, KIR-HLA-mismatched group included 42 cases and the matched group included 5 cases. KIR-HLA-mismatched group had higher 2-year disease-free sur- Vival （DFS） rate compared with KIR-HLA-matched group [ （71.5 ±6.5）% vs. （50.0± 10.7）%, P 〈 0. 05 ]. Conclusions The rate of activating KIR is lower than inhibitory KIRs. Inhibitory KIR2DL1, 3DL1, and 3DL2 may play key roles in the natural killer cell alloreactivity. The DFS rate is higher in KIR-HLA-mismatched group than in KIR-HLA-matched group in related donor HSCT.