重型再生障碍性贫血患儿免疫抑制治疗疗效及T细胞亚群变化的临床分析  

Clinical analysis of curative effect and change of T cell subsets in children with severe aplastic anemia following immunosuppressive therapy

作　　者：陈慧 马洁[1] 邢天禹 赵晓曦[1] 田硕[1] 高超[1] 陈振萍[1] Chen Hui;Ma Jie;Xing Tianyu;Zhao Xiaoxi;Tian Shuo;Gao Chao;Chen Zhenping(Hematologic Disease Laboratory,Hematology Center,Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in Children,Ministry of Education Beijing Pediatric Research Institute,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心、首都医科大学附属北京儿童医院血液病中心、儿童血液病与肿瘤分子分型北京市重点实验室、儿科学国家重点学科、儿科重大疾病研究教育部重点实验室、北京市儿科研究所、血液疾病研究室,北京100045

出　　处：《国际输血及血液学杂志》2022年第3期229-237,共9页International Journal of Blood Transfusion and Hematology

基　　金：国家自然科学基金(81970111);北京市自然科学基金(7192064);国家科技重大专项(2017ZX09304029001)。

摘　　要：目的探讨免疫抑制治疗(IST)应用于儿童获得性重型再生障碍性贫血(SAA)/极重型再生障碍性贫血(VSAA)的疗效及对其T细胞亚群的影响。方法选择2017年7月至2019年9月,北京儿童医院血液病中心收治的采取IST的35例SAA和15例VSAA患儿为研究对象。其中,男性患儿为33例,女性为17例,中位年龄为9岁(2~14岁)。对患儿均采取抗胸腺细胞球蛋白(ATG)联合环孢素的IST。回顾性收集患儿接受IST后的疗效,以及IST前,治疗后3、6、12个月时流式细胞术(FCM)检测的T细胞亚群比例。对SAA与VSAA患儿T细胞亚群比例比较,采用t检验或者Wilcoxon秩和检验,达完全缓解(CR)、部分缓解(PR)与未缓解患儿T细胞亚群比例比较,采用完全随机设计资料的方差分析或者Kruskal-Wallis H检验;达CR患儿IST前与治疗后12个月时T细胞亚群比例比较,采用配对t检验或者Wilcoxon符号秩和检验。对血液学缓解与未缓解患儿IST前、治疗后3、6、12个月时调节性T细胞(Treg)比例比较,采用重复测量资料的方差分析。对血液学缓解患儿IST前、治疗后3、6、12个月时Treg比例两两比较采用LSD-t法。本研究符合2013年修订的《世界医学会赫尔辛基宣言》要求,并征得受试者及其监护人知情同意。结果①全部SAA/VSAA患儿中位随访时间为12个月(10.5个月,24.0个月)。截至末次随访时间,2例患者失访,其余48例患者中,39例(81.3%)经IST达血液学缓解,其中CR为28例,PR为11例;9例(18.8%)未缓解。②SAA与VSAA患儿IST前各T细胞亚群比例分别比较,差异均无统计学意义(P>0.05)。治疗后达CR(n=28)、PR(n=11)和未缓解(n=9)的SAA/VSAA患儿治疗前各T细胞亚群比例分别比较,差异亦均无统计学意义(P>0.05)。③与IST前相比较,治疗后12个月时达CR(n=22)的SAA/VSAA患儿CD3^(+)T细胞[74.5%(63.4%,78.6%)比62.0%(50.8%,72.9%),Z=-2.197,P=0.028],CD3^(+)CD4^(+)T细胞[(48.1±3.2)%比(41.2±1.8)%,t=2.240,P=0.034]及Treg比例均显著下降[6.8%Objective To investigate curative effect of immunosuppressive therapy(IST)and its influence on T cell subsets in children with acquired severe aplastic anemia(SAA)/very severe aplastic anemia(VSAA).Methods From July 2017 to September 2019,a total 50 cases of newly diagnosed SAA/VSAA children who were admitted to Hematology Center,Beijing Children′s Hospital and receiving IST were selected as research subjects.Among them,33 cases were male and 17 were female,with a median age of 9 years(2-14 years).35 cases met SAA diagnosis criteria and 15 meeting VSAA diagnosis criteria.All children received IST of anti-thymocyte globulin(ATG)combined with cyclosporin treatment.Efficacy of IST and proportion of T cell subsets detected by flow cytometry(FCM)before and 3,6,and 12 months after IST were analysed retrospectively.Proportions of T cell subsets in children with SAA or VSAA were compared using t test or Wilcoxon rank-sum test.Proportions of T cell subsets in children with complete remission(CR),partial remission(PR)and non-remission were compared using completely random design analysis of variance or Kruskal-Wallis H test.Proportions of T cell subsets before and 12 months after IST in children with CR were compared using paired t test or Wilcoxon signed-rank sum test.Proportions of regulatory T cells(Treg)in children with hematologic remission and those without remission were compared before and 3,6,and 12 months after IST by repeated measures analysis of variance.LSD-t method was used in pairwise comparison of proportions of Treg before and 3,6 and 12 months after IST in children with hematologic remission.This study was conducted in accordance with the World Medical Asslciation revised in 2013,and the informed consents were obtained from the subjects and their guardians.Results①Median follow-up time of all cases of SAA/VSAA children was 12 months(10.5 months,24.0 months).Up to the last follow-up,2 cases were lost.Among the remaining 48 cases,39 cases(81.3%)achieved hematologic remission by IST,including 28 cases of

关 键 词：T淋巴细胞 调节性 T淋巴细胞 辅助诱导 T淋巴细胞亚群 免疫抑制治疗 再生障碍性贫血 儿童 

分 类 号：R725.5[医药卫生—儿科]