摘要
目的 探讨儿童造血干细胞移植(HSCT)后12个月内细胞免疫重建规律及其与移植物抗宿主病(GVHD)发生的相关性.方法 收集26例行HSCT的血液病患儿一般临床资料(性别、移植年龄、诊断、移植方案、感染及GVHD预防方案、CD34+细胞及单个核细胞细胞输注量),随访6~12月,抽取患儿HSCT后第1、3、6、9及12月外周血,采用六色直接免疫荧光法检测外周血中淋巴细胞亚群CD3+T细胞、CD4+T细胞、CD8+T细胞、CD4/CD8、CD19+B细胞、自然杀伤(NK)细胞水平,采用单因素及多因素分析HSCT后各免疫细胞水平与GVHD发生的相关性.结果 除CD4+T细胞、CD4/CD8比值外,其余淋巴细胞均达免疫重建,其中CD8+T细胞重建最快,1~3月达正常水平;26例患儿中急性GVHD 8例(30.8%),慢性GVHD 23例(88.4%);单因素分析显示,患儿HSCT后第1、6、9个月CD3+T细胞水平,第1及6月CD4+T细胞水平,第1及9月CD8+T细胞水平与慢性GVHD的发生率有相关性(P<0.05);多因素分析显示,患儿HSCT后6个月CD4+T细胞水平与慢性GVHD发生率呈负相关(P<0.05).结论 HSCT后细胞免疫重建速度由快到慢依次为CD8+T细胞、NK细胞、CD19+B细胞、CD3+T细胞及CD4+T细胞,12月时CD4/CD8比值倒置但已趋近于正常值下限;CD4+T细胞的重建延迟与慢性GVHD的发生密切相关.
Abstract
Objective To investigate the patterns of cellular immune reconstitution within 12 months after hematopoietic stem cell transplantation(HSCT)in pediatric patients and its correlation with the occurrence of graft-versus-host disease(GVHD).Methods Clinical data(gender,age at transplantation,diagnosis,transplantation regimen,infection and GVHD prevention regimen,infusion amount of CD34+cells and mononuclear cells[MNC])were collected from 26 pediatric patients undergoing HSCT.Follow-up was conducted for 6-12 months,with peripheral blood samples taken at 1,3,6,9,and 12 months post-HSCT.Six-color direct immunofluorescence was used to detect levels of peripheral blood lymphocyte subsets,including CD3+T cells,CD4+T cells,CD8+T cells,CD4/CD8 ratio,CD19+B cells,and natural killer(NK)cells.Univariate and multivariate analyses were performed to assess the correlation between levels of these immune cells post-HSCT and the occurrence of GVHD.Results Except for CD4+T cells and CD4/CD8 ratio,all lymphocyte subsets achieved immune reconstitution,with CD8+T cells reconstituting the fastest,reaching normal levels within 1-3 months.Among the 26 patients,8(30.8%)developed acute GVHD(a-GVHD),and 23(88.4%)developed chronic GVHD(c-GVHD).Univariate analysis showed that levels of CD3+T cells at 1,6,and 9 months,levels of CD4+T cells at 1 and 6 months,and levels of CD8+T cells at 1 and 9 months post-HSCT were correlated with the incidence of c-GVHD(P<0.05).Multivariate analysis indicated that the level of CD4+T cells at 6 months post-HSCT was negatively correlated with the incidence of c-GVHD(P<0.05).Conclusion The speed of cellular immune reconstitution post-HSCT from fastest to slowest is CD8+T cells,NK cells,CD19+B cells,CD3+T cells,and CD4+T cells.At 12 months,the CD4/CD8 ratio is inverted but approaching the lower limit of normal values.Delayed reconstitution of CD4+T cells is closely associated with the occurrence of c-GVHD.
基金项目
贵州省科技计划项目(黔科合平台人才[2019]5406)