异基因造血干细胞移植受者外周血中可溶性HLA-G与急性GVHD的相关性

目的 探讨异基因造血干细胞移植(allo-HSCT)受者外周血中可溶性HLA-G(sHLA-G)的水平与急性移植物抗宿主病(aGVHD)间的相关性以及与CD4+CD25~(hlgh)调节性T淋巴细胞(Treg)水平的相关性.方法 选择27例allo-HSCT受者,将其中13例术后发生aGVHD者作为aGVHD组,14例未发生aGVHD者作为对照组.在移植预处理前、移植后第2、4、8、14周时,分别抽取两组受者清晨空腹肘静脉血2～4 ml,采用酶联免疫吸附试验双抗夹心法定量检测sHLA-G,采用流式细胞术检测CD4+CD25+Treg.动态监测术后第2和14周受者sHLA-G水平的变化;动态监测和分析术后第8和14周两组受者间sHLA-G的差异.观察sHLA-G与发生aGVHD的相关性;检测术后第14周两组受者CD4+CD25+Treg的数量,观察sHLA-G水平与CD4+CD25+Treg的相关性.结果 预处理前,对照组和aGVHD组受者sHLA-G的水平分别为(75.4±13.1)/μg/L和(47.0±14.1)btg/L,两组间差异有统计学意义(P<0.05).术后第8周和第14周,对照组受者sHLA-G的水平明显高于相应时间点aGVHD组受者,两组间差异均有统计学意义(P<0.01).对照组受者术后第14周的sHLA-G水平与第2周相比,增长了1.2～3.4倍,两时间点的差异有统计学意义(P<0.05).术后第14周,通过Spearman等级相关检验显示受者sHLA_G水平与CD4+CD25+Treg比例具有统计学上的相关性(相关系数r=0.810,P<0.05),结论 allo-HSCT后受者体内sHIA-G对aGVHD的发生起负性调节作用;sHLA-G的水平与外周血CD4+CD25~(hlgh) T淋巴细胞的比例旱正相关,二者之间可能存在相互诱导和调节的信号途径,在诱导和维持移植免疫耐受中起着重要的协同作用.

The correlation between soluble HLA-G and acute graft-versus-host disease after allo-geneic hematopoietic stem cell transplantation

Objective To explore the effect of sHLA-G on acute GVHD(aGVHD) and the relationship between the level of sHLA-G and the number of CD4+ CD25~(hlgh)T cells (Treg) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Among 27 cases of allo-HSCT recipients, 13 of them with aGVHD served as aGVHD group, and the rest 14 as control group.Before and at the 2nd, 4th, 8th, 14th week after transplantation, 2-4 ml blood was obtained from elbow veins in the early morning, double-antibody sandwich of enzyme-linked immunosorbent assay was used for quantification of sHLA-G, and flow cytometry for dynamic determination of the number of CD4~+ CD25~+ Treg.The levels of sHLA-G at the 8th and 14th week after transplantation in the recipients were measured, and the relationship between the sHLA-G and the occurrence of aGVHD was analyzed.By detecting the number of CD4~+ CD25~+ Treg from two recipients groups at the 14th week, the relevance between the level of sHLA-G and the number of CD4+ CD25+ Treg was observed.Results Before transplantation, the levels of sHLA-G in the control group and aGVHD group were (75.4±13.1 ) and (47.0±14.1 ) μg/L respectively with the difference being statistically significant (P<0.05).At the 8th and 14th week after transplantation, the levels of sHLA-G in the control group were significantly higher than in the aGVHD group at the corresponding time points with the difference being statistically significant (P<0.01 ).In the control group, the levels of sHLA-G at the 14th week were increased by 1.2-3.4 times, compared with those at the 2nd week (P.< 0.05).At the 14th week, Spearman rank correlation tests revealed that there was a statistical correlation between the levels of sHLA-G from the recipients and the proportion of CD4+ CD25+ Treg (correlation coefficient was 0.810, P<0.05).Conclusion The plasma sHLA-G in patients after allo-HSCT plays a negative regulatory role in the occurrence of aGVHD.There is a positive correlation between the levels of sHLA-G and the proportion of CD4+ CD25~(hlgh)Treg in peripheral blood.There may exist induction and regulation of molecules through the cell signaling pathways between sHLA-G and CD4+ CD25~(hlgh) Treg, which can synergically induce and maintain transplant immune tolerance.