摘要
本研究探讨异源反应性NK细胞免疫球蛋白样受体(KIR)与HLA配体的关系对非去T细胞异基因造血干细胞移植(allo-HSCT)预后的影响。应用序列特异性引物分型技术检测供受者的KIR及HLA基因型,并对我院67例接受非去T细胞allo-HSCT的病例资料进行回顾性分析。根据供者KIR及受者HLA关系及供者是否表达活化性KIR进行分组,通过单因素及多因素分析确定抑制性及活化性KIR基因对移植预后的影响。结果表明,抑制性KIR/配体相合组无事件生存率(EFS)略高于不合组,其中KIR2DL1/C2相合组3年EFS显著高于C2不相合组(69.2%vs 44.8%,P=0.043),而抑制性KIR/配体相合组的复发率、急性GVHD发生率及移植相关死亡率(TRM)与不合组无显著差异。供者表达活化性KIR2DS2的患者,其3年EFS更高(81.3%vs 52.6%,P=0.05),且复发率显著减低(7.7%vs 34.2%,P=0.05)。而受者不表达C2组配体时,供者表达活化性KIR2DS1的患者,即KIR2DS1阳性/HLA-C2阴性组,其3年EFS明显下降(P=0.028),急性GVHD发生率明显上升(P=0.028)。多因素分析表明,疾病进展期、活化受体数目增多、供者不表达KIR2DS2表型是生存率下降的独立危险因素(HR=3.34、2.19、3.18;95%CI=1.43-7.82、0.99-4.83、0.93-11;P=0.005,0.053,0.066)。此外,疾病进展期、供者不表达KIR2DS2表型也是高复发率的独立危险因素(HR=6.72,9.43;95%CI为1.36-33.16,1.03-8.33;P=0.019,0.047)。而供者KIR2DS1阳性/受者HLA-C2阴性是移植相关死亡的唯一危险因素(HR=3.27,95%CI1.78-9.06,P=0.023)。结论:在非去T细胞allo-HSCT中,抑制性KIR/HLA不合对移植后患者生存率、疾病复发率及TRM的影响较小,但可能干扰移植早期抗病毒免疫。抑制性KIR2DL1/HLA C2不合组EFS显著低于相合组,这可能与该组患者TRM上升、急性GVHD发生率升高有关。而活化性KIR对患者EFS、复发及急性GVHD发生率都有影响。供者不表达KIR2DS2预示着生存期延长,这与复发率低有关,而供者KIR2DS1阳性/受�
This study was purposed to investigate the role of NK-aUoreactivity and donor-inhibiting or activating K1R gene in predicting prognosis under unmanipulated allogeneic blood and marrow transplantation. A modified polymerase chain reaction sequence specific primers （PCR-SSP） method was used to typing K/R and HLA genotype of donors and recipients. The relationship between donor activating or inhibitory K/R and recipient HLA genotypes on event free survival （EFS）, cumulative incidence of malignant relapse and transplant-related mortality （TRM） were investigated retrospectively in 67 patients undergoing hematopoietic stem cell transplantation. The results showed that no effect of＇ K/R/HLA mismatched＇ was detected on acute graft-versus-host disease （aGVHD） and relapse. The EFS of KIR/HLA mismatched group was lower, especially KIR2DL1/HLA-C2 mismatched group （44.8 % vs 69. 2 %, P = 0.043 ）. However, EFS was better for the presence of donor-activating KIR2DS2 （ 81. 3% vs 52. 6%, P = 0. 052 ）, and the relapse rate was significantly lower for the presence of this genotype （ 7. 7% vs 34. 2%, P = 0. 05 ）. EFS was worse in patients homozygous for group 1 HLA-C （ C1 ） when donor carries the activating KIR2DS1 （ KIR2DSI positive/HLA-C2-negative group, P = 0.028 ）, and the incidence of aGVHD in this group was significantly higher than that in any other groups （P = 0.028）. In multivariate analysis, advanced disease stage, more than two donor-activating KIR, donor KIR2DS2- negative genotype were associated with an reduced disease-free survival （ HR = 3.34, 2. 19, 3. 18 ; and P = 0. 005, 0.053,0. 066）. Donor KIR2DS2-negative genotype were also associated with an increased risk of relapse（ HR = 6.72, 9.43 ;and P = 0.019,0.047）. And donor KIR2DS1 positive/reciepient HLA-C2 nagative group was the only risk factor of TRM （HR = 3.27, 95% CI 1.78 -9.06, P = 0.023 ）. It is concluded that missing ligand for the donor inhibitory K/R has weak effect on the outcome of unmanipulated HSCT.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2013年第1期155-160,共6页
Journal of Experimental Hematology
基金
国家自然科学基金项目(编号30940030
81070448)
卫生行业科研专项基金(编号201220217)
