摘要目的 研究髓系来源抑制细胞(MDSC)在异基因造血干细胞移植(allo-HSCT)受者中的变化规律,探讨MDSC的增殖与allo-HSCT受者急性移植物抗宿主病(GVHD)的发生及临床预后的相关性.方法 收集30例allo-HSCT的白血病患者及10位健康志愿者的外周血标本,每次用肝素抗凝管留取血6ml.采集allo-HSCT受者输注的造血干细胞及移植后100 d内的外周血,流式细胞学检测MDSC的表达变化;用酶联免疫吸附测定(Elisa)法检测白细胞介素6(IL-6),IL-10,IL-1β,肿瘤坏死因子(TNF-α),精氨酸酶-1(Arg-1),血红素氧合酶-1(HO-1),诱导性一氧化氮合酶(iNOS)的水平.结果 移植后,发生急性GVHD受者回输的干细胞中MDSC的数量[(39.94±8.383)×106/kg]明显低于未发生急性GVHD受者[(209.0±57.68)×106/kg,P=0.002 6];未发生急性GVHD的受者回输的MDSC数目[(209.0±57.68)×106/kg]明显高于发生Ⅲ～Ⅳ度急性GVHD的受者[(20.37±4.304)×106/kg,P=0.013 9].发生急性GVHD的受者外周血中MDSC比例[(7.725±1.460)％]明显高于未发生急性GVHD的受者[(3.423±1.044)％,P=0.021 3].回输干细胞中MDSC数目＞53.712×106/kg的患者预后明显优于回输干细胞中MDSC数目≤53.712×106/kg的患者,受者2年总存活率(OS)分别为100％和50％,P=0.001 3,2年复发率分别为6.250％和29.252％,P=0.112 3,非复发死亡率分别0％和9.519％,P=0.001 8.移植后,急性GVHD发生会伴随MDSC比例的增高,IL-6、IL-10及TNF-α的浓度及免疫相关蛋白Arg-1、iNOS和HO-1的水平也明显增高.结论 干细胞回输时MDSC的数目及植活时外周血中MDSC水平可作为预测异基因造血干细胞移植后急性GVHD的发生及严重程度的指标;回输MDSC或促进MDSC的扩增可能是一个减轻移植后急性GVHD的有效方法.

abstractsObjective In order to evaluate the possible effects of myeloid-derived suppressor cells (MDSCs) on graft versus host disease (aGVHD) development and clinical outcomes,this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Peripheral blood was obtained from 30 patients and 10 healthy volunteers with heparin anticoagulant tubes for 6 mL.For patients,peripheral blood was collected during the first 100 days after allo-HSCT and MDSCs levels were detected by flow cytometry.For measuring the serum concentrations of IL-6,IL-10,IL-1β,TNF-α,Arg-1,HO-1 and iNOS,samples were analyzed using ELISA kits.Results Patients developing aGVHD were infused with significantly less number of MDSCs [(39.94 ± 8.383) 106/kg]than in those not developing aGVHD [(209.0 ± 57.68) 106/kg,P =0.002 6];Patients developing aGVHD Ⅰ-Ⅱ and patients without aGVHD received significantly greater number of MDSCs [(61.96 ± 13.67) 106/kg and (209.0 ± 57.68) 106/kg] than in those developing aGVHD Ⅲ-Ⅳ [(20.37 ±4.304) 106/kg,P =0.013 9].After allo-HSCT,the mean percentage of MDSCs increased markedly in patients developing aGVHD [(7.725 ± 1.460)％] as compared with those not developing aGVHD [(3.423± 1.044)％,P =0.021 3].The high MDSCs group (＞53.712 × 106/kg) showed more favorable clinical outcomes than in the low MDSCs group (≤53.712 × 106/kg).The 2-year overall survival rate as 100％ in high MDSCs group,and 50％ in low MDSCs group (P =0.001 3).The cumulative incidence of 2-year relapse was 6.250％ and 29.252％ in high MDSCs group and low MDSCs group respectively (P =0.112 3).The cumulative incidence of NRM was significantly lower in high MDSCs group (0％) than in low MDSCs group (49.519％,P=0.001 8).MDSCs frequencies significantly increased in patients developing aGVHD after allo-HSCT.After allo-HSCT,the concentrations of IL-6,IL-10,TNF-α,Arg-1,iNOS and HO-1 were significantly elevated in patients developing aGVHD.Conclusion The number of MDSCs when engraftment may be used as a predictor for the development and severity of aGVHD.MDSCs might be considered as a potential new approach to regulate transplant rejection and achieve long-term survival.