血液病患儿造血干细胞移植后细胞免疫重建规律及其与移植物抗宿主病发生的相关性  

Patterns of cellular immune reconstitution after hematopoietic stem cell transplantation in pediatric hematological patients and its correlation with the occurrence of graft-versus-host disease

作　　者：杨玉婷 金皎 马健娟 王一慧 黄璟 YANG Yuting;JIN Jiao;MA Jianjuan;WANG Yihui;HUANG Jing(Department of Pediatric Hematology,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Clinical Medicine,Guizhou Medical University,Guiyang 550001,Guizhou,China)

机构地区：[1]贵州医科大学附属医院儿童血液科,贵州贵阳550004 [2]贵州医科大学临床医学院,贵州贵阳550001

出　　处：《贵州医科大学学报》2024年第9期1360-1365,共6页Journal of Guizhou Medical University

基　　金：贵州省科技计划项目(黔科合平台人才〔2019〕5406)。

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。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.

关 键 词：儿童 淋巴细胞 移植物抗宿主病 造血干细胞移植 免疫重建 临床并发症 

分 类 号：R745.5[医药卫生—神经病学与精神病学]