自然杀伤细胞免疫球蛋白样受体在脐带血移植治疗白血病中的作用

Killer cell immunoglobulin receptor plays an important role in cord blood transplantation for leukemia

目的探讨自然杀伤细胞免疫球蛋白样受体(KIR)在脐带血移植中的作用。方法总结23例脐带血移植治疗白血病病例,应用序列特异引物聚合酶链反应(PCR-SSP)基因分型方法,检测患者外周血和脐带血的人类白细胞抗原(HLA)-C等位基因分型和KIR基因分型,随访其植活率和长期生存率,分析KIR对脐带血移植的影响和产生的作用。结果通过检测发现KIR基因在23位供者中的表达呈现多态性。在17例髓性白血病组中,如果供受双方KIR抑制性受体与其配体HLA-C不匹配,其植活率和长期生存率高于匹配组(64%vs50%,73%vs50%),且复发率降低(9%vs16%)。如果患者HLA-Cw1或HLA-Cw2亚群缺失,其移植后的植活率和长期生存率长于HLA-Cw1/Cw2双表达组(65%vs50%,70%vs50%)。HLA-Cw8(+)对于预后的影响与不含Cw8组并无明显区别。KIR2DL2与KIR2DS2呈连锁表达,供者中其双表达共4例移植病例全部长期无病生存。结论KIR及其配体HLA-C对脐带血移植治疗白血病起到重要作用。供受双方KIR/HLA-C不匹配组,患者HLA-Cw1或HLA-Cw2亚群缺失组,供者KIR2DL2与KIR2DS2双表达组提示预后好。

Objective To investigate the role of killer cell immunoglobulin receptor （KIR） plays in treatment of leukemia by cord blood transplantation （CBT）. Methods Peripheral blood samples were collected from 23 patients receiving CBT, and corresponding cord blood samples were collected too. Polymerase chain reaction with sequence-specific primers was used to examine the genotypes of KIR and HLA-Cw of the samples. The rates of engraftment, relapse, and survival were followed up. Results Polymorphism of KIR genotype was found in the 23 cord blood samples. In the 17 cases of acute myelocytic leukemia （AML） , the engraftment rate and overall survival rate of the donors/recipients with KIR/JHLA-C mismatch was 65% and 70%, both higher than those of the KIR/HLA-C matched group （50% and 50% respectively）, and the relapse rate of those with KIR/JHLA-C mismatch was 9%, lower than that of the KIR/HLA-C matched group （16%）. The engraftment rate and overall survival rate of those with homoexpression of HLA-Cw1 or Cw2 were 65% and 70% respectively, both higher than those of the patients with double expression （50% and 50% respectively）. There was no significant difference in overall survival rate between the HLA-Cw8 （ ＋ ） and HLA-Cw8 （ - ） groups. Four cases with the co-expression of KIR2DL2 and KIR2DS2 all survived disease-free. Conclusion KIR plays an important role in CBT. KIR/HLA-C mismatch, homo-expression of HLA-Cwl or Cw2, and co-expression of KIR2DL2 and KIR2DS2 may predict good prognosis for CBT.