重症流行性感冒患者T淋巴细胞与预后研究  

Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza

作　　者：耿陶然[1] 韩扬[1] 邱志峰[1] 杜铁宽[2] 江伟[3] 施举红[4] 秦天[5] 范洪伟[1] 李太生[1,6] Geng Taoran;Han Yang;Qiu Zhifeng;Du Tiekuan;Jiang Wei;Shi Juhong;Qin Tian;Fan Hongwei;Li Taisheng(Department of Infectious Diseases,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;Emergency Department,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;Medical Intensive Care Unit,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Respiration,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;Clinical Immunology Center,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院感染科,100730 [2]中国医学科学院,北京协和医学院,北京协和医院急诊科,100730 [3]中国医学科学院,北京协和医学院,北京协和医院内科ICU,100730 [4]中国医学科学院,北京协和医学院,北京协和医院呼吸科,100730 [5]中国疾病预防控制中心传染病预防控制所,北京102206 [6]中国医学科学院临床免疫研究中心,北京100730

出　　处：《中华内科杂志》2020年第3期200-206,共7页Chinese Journal of Internal Medicine

基　　金：中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-014);重要新发突发传染病生物安全基础与防控技术研究(2016-I2M-1-014)。

摘　　要：目的研究重症流行性感冒(流感)患者外周血T淋巴细胞亚群的特点及与预后相关的因素。方法本研究为单中心横断面研究,选取2017年8月至2018年4月于北京协和医院住院的流感患者。选取体检中心年龄匹配的108名健康体检者作为对照组。将流感患者按轻症、重症及重症存活、重症死亡分组,比较流感患者与健康对照及不同组流感患者的临床及淋巴细胞亚群特点。运用流式细胞仪检测外周血淋巴细胞亚群。结果研究共纳入42例流感患者,其中重症24例(死亡6例),轻症18例。流感患者总体的外周血淋巴细胞[699(505,1093)个/μl比1963(1603,2394)个/μl]、B细胞[75(37,140)个/μl比179(119,239)个/μl]、自然杀伤(NK细胞)[64(37,133)个/μl比356(231,496)个/μl]、CD4^+T细胞[353(237,505)个μl比663(531,824)个/μl]及CD8^+T细胞[210(126,348)个/μl比481(341,693)个/μl]均显著低于健康对照组(P值均<0.001);且重症死亡组的T细胞总数和CD8^+T细胞计数显著少于存活组[T细胞总数370(260,537)个/μl比722(390,990)个/μl,P<0.05;CD8^+T细胞计数87(74,105)个/μl比222(154,404)个/μl,P值均<0.01]。CD8^+T细胞激活指标CD8^+HLA-DR/CD8^+轻症组明显高于重症组[(53.7±19.2)%比(38.5±21.7)%,P<0.05];重症存活组明显高于重症死亡组[(46.1±19.1)%比(18.2±14.6)%,P<0.01];CD8^+CD38^+/CD8^+轻症组明显高于重症组[74.8%(64.1%,83.7%)比53.3%(45.3%,67.2%),P<0.01]。回归分析显示CD8^+T细胞计数(OR=0.952,95%CI 0.910~0.997,P=0.035)及CD8^+HLA-DR/CD8^+T比例(OR=0.916,95%CI 0.850~0.987,P=0.022)与重症流感患者的病死率呈负相关。动态监测血常规可见轻症患者起病后1 d内外周血淋巴细胞计数大幅下降,平均降幅57.0%,但在病后1周即能基本回升至原先水平。结论流感患者病程中外周血淋巴细胞各亚群数量显著减低,重症患者CD8^+T细胞在外周血中的计数和激活水平与死亡风险呈负相关趋势,有望作为预估重症流感患者预后的指Objective To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza.Methods This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018.Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls.Influenza patients were divided into mild group and severe group.Severe patients were further classified into alive and fatal subgroups.Results A total of 42 influenza patients were recruited in this study,including 24 severe cases(6 deaths).The remaining 18 cases were mild.The peripheral blood lymphocyte counts and lymphocyte subset counts(B,NK,CD4^+T,CD8^+T)in either mild patients[795(571,1007),43(23,144),70(47,135),330(256,457),226(148,366)cells/μl respectively]or severe patients[661(474,1151),92(52,139),54(34,134),373(235,555),180(105,310)cells/μl respectively]were both significantly lower than those of healthy controls[1963(1603,2394),179(119,239),356(231,496),663(531,824),481(341,693)cells/μl respectively].Meanwhile,the T cells and CD8^+T counts in fatal patients[370(260,537)cells/μl and 87(74,105)cells/μl]were significantly lower than those in severe and alive patients[722(390,990)cells/μl and 222(154,404)cells/μl].CD8^+HLA-DR/CD8^+ and CD8^+CD38^+/CD8^+T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8%(64.1%,83.7%)respectively]were significantly higher than those in severe cases[(38.5±21.7)% and 53.3%(45.3%,67.2%)respectively].Moreover,CD8^+ HLA-DR/CD8^+ count in severe and alive group was higher than that in fatal group[(46.1±19.1)%vs.(18.2±14.6)%,P<0.01].Logistic regression analysis showed that CD8^+T cell count(OR=0.952,95%CI 0.910-0.997,P=0.035)and CD8^+ HLA-DR/CD8^+T(OR=0.916,95% CI 0.850-0.987,P=0.022)were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis,and returned to the basic level

关 键 词：流感 人 重症 淋巴细胞亚群 CD8^+T细胞 激活亚群 

分 类 号：R51[医药卫生—内科学]