人巨细胞病毒感染对异基因造血干细胞移植患儿CD8^(+)T细胞免疫重建的影响  

Effect of HCMV infection on immune reconstitution of CD8^(+)T cells in children with allogeneic hematopoietic stem cell transplantation

作　　者：魏泽 冯顺乔[2] 易小钰 罗琴 杜海军[4] 梅国勇 刘嵘[3] 姚海兰[2] 韩俊 Wei Ze;Feng Shunqiao;Yi Xiaoyu;Luo Qin;Du Haijun;Mei Guoyong;Liu Rong;Yao Hailan;Han Jun(School of Public Health Baotou Medical College,Baotou 010404,China;Department of Hematology,Children′s Hospital of Capital Institute of Pediatrics,Beijing 100020,China;Department of Biochemistry&Immunology,Capital Institute of Pediatrics,Beijing 100020,China;National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute of Viral Disease Control and Prevention,Beijing 102206,China)

机构地区：[1]包头医学院公共卫生学院,包头010404 [2]首都儿科研究所附属儿童医院血液科,北京100020 [3]首都儿科研究所生化免疫研究室,北京100020 [4]中国疾病预防控制中心病毒病预防控制所传染病溯源预警与智能决策全国重点实验室,北京102206

出　　处：《中华预防医学杂志》2023年第12期2095-2101,共7页Chinese Journal of Preventive Medicine

基　　金：人类病毒感染事件综合应对技术体系及标准规范(2022YFC2602402);首都儿科研究所临床检测研究专项基金(CTR-2023-003);国家病原微生物资源库(NPRC-32)。

摘　　要：目的探讨儿童异基因造血干细胞移植(allo-HSCT)后人巨细胞病毒感染的危险因素以及人巨细胞病毒感染对移植后免疫重建的影响。方法采用回顾性队列研究设计,将2020年1月至2022年3月在北京首都儿科研究所血液科接受allo-HSCT治疗的81例患儿纳入研究,并随访1年。采用实时荧光定量PCR方法检测患儿allo-HSCT后的人巨细胞病毒(HCMV)的阳性检出情况,采用多因素logistic回归模型分析导致HCMV感染的危险因素,并采用广义估计方程模型分析HCMV感染对接受allo-HSCT后患儿T细胞的影响。结果81例患儿年龄M(Q_(1),Q_(3))为5.1岁(10个月,13.8岁),男性50例(61.7%)。截至随访终点,共检出HCMV阳性50例,HCMV检出率为61.7%。多因素logistic回归模型结果显示,与移植后0~1级相比,2~4级aGVHD患儿HCMV感染风险较高[OR(95%CI)值:2.735(1.027~7.286)]。广义估计方程模型分析结果显示,移植后HCMV阳性患儿CD3+T细胞数量高于HCMV阴性组[RR(95%CI)值:1.34(1.008~1.795)];CD4^(+)T/CD8^(+)T细胞比值小于HCMV阴性组[RR(95%CI)值:0.377(0.202~0.704)];CD8^(+)T细胞数高于HCMV阴性组[RR(95%CI)值:1.435(1.025~2.061)];效应记忆型CD8^(+)T细胞数量高于HCMV阴性组[RR(95%CI)值:1.877(1.089~3.236)]。结论急性移植物抗宿主病可能是导致allo-HSCT后患儿感染HCMV的危险因素;移植后HCMV感染促进了记忆型CD8^(+)T细胞数量增殖,影响免疫细胞重建。Objective To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution.Methods A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology,Capital Institute of Pediatrics,Beijing,China,and followed up for 1 year.Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT,multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection,and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT.Results The age M(Q_(1),Q_(3))of 81 children was 5.1 years(10 months,13.8 years),and 50(61.7%)were male.By the endpoint of follow-up,a total of 50 HCMV-positive cases were detected,with an HCMV detection rate of 61.7%;The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation[OR(95%CI)value 2.735(1.027-7.286)].The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group[RR(95%CI)value 1.34(1.008-1.795)];the ratio of CD4^(+)T/CD8^(+)T cells was smaller than that in the HCMV-negative group[RR(95%CI)value 0.377(0.202-0.704)];the number of CD8^(+)T cells was higher than that in the HCMV-negative group[RR(95%CI)value 1.435(1.025-2.061)];the number of effector memory CD8^(+)T cells was higher than that in the HCMV-negative group[RR(95%CI)value 1.877(1.089-3.236)].Conclusion Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT;post-transplant HCMV infection promotes proliferation of memory CD8^(+)T-cel

关 键 词：异基因造血干细胞移植 儿童 人巨细胞病毒 免疫重建 

分 类 号：R725[医药卫生—儿科]