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[重症流感患者外周血T淋巴细胞亚群的特征及预后价值]

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

作者信息

Geng T R, Han Y, Qiu Z F, Du T K, Jiang W, Shi J H, Qin T, Fan H W, Li T S

机构信息

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.

出版信息

Zhonghua Nei Ke Za Zhi. 2020 Mar 1;59(3):200-206. doi: 10.3760/cma.j.issn.0578-1426.2020.03.006.

Abstract

To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. 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. 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 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),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)%, 0.01]. Logistic regression analysis showed that CD8(+)T cell count (0.952, 95 0.910-0.997, 0.035) and CD8(+)HLA-DR/CD8(+)T (0.916, 95 0.850-0.987, 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 one week later. All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8(+)T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

摘要

探讨重症流感患者外周血T淋巴细胞亚群的特征及预后价值。本研究为单中心横断面研究,纳入了2017年8月至2018年4月在北京协和医院住院的流感患者。采用流式细胞术检测患者及108名健康对照者外周血淋巴细胞亚群。流感患者分为轻症组和重症组,重症患者进一步分为存活亚组和死亡亚组。本研究共纳入42例流感患者,其中24例为重症(6例死亡),其余18例为轻症。轻症患者外周血淋巴细胞计数及淋巴细胞亚群计数(B细胞、NK细胞、CD4(+)T细胞、CD8(+)T细胞)[分别为795(571,1 007)、43(23,144)、70(47,135)、330(256,457)、226(148,366)个/μl]及重症患者[分别为661(474,1 151)、92(52,139)、54(34,134)、373(235,555)、180(105,310)个/μl]均显著低于健康对照者[分别为1 963(1 603,2 394)、179(119,239)、356(231,496)、663(531,824)、481(341,693)个/μl]。同时,死亡患者的T细胞及CD8(+)T细胞计数[分别为370(260,537)个/μl和87(74,105)个/μl]显著低于重症存活患者[分别为722((390,990)个/μl和222(154,404)个/μl]。轻症患者CD8(+)HLA-DR/CD8(+)及CD8(+)CD38(+)/CD8(+)T细胞活化亚群比例[分别为(53.7±19.2)%和74.8%(64.l%,83.7%)]显著高于重症患者[分别为(38.5±21.7)%和53.3%(45.3%,67.2%)]。此外,重症存活组CD8(+)HLA-DR/CD8(+)比例高于死亡组[(46.l±19.l)% 对 (18.2±14.6)%,P = 0.01]。Logistic回归分析显示,CD8(+)T细胞计数(0.952,95%CI 0.910 - 0.997,P = 0.035)及CD8(+)HLA-DR/CD8(+)T比例(0.916,95%CI 0.850 - 0.987,P = 0.022)均与死亡率呈负相关。轻症患者外周血淋巴细胞计数在诊断后1天内迅速下降,1周后恢复至基线水平。流感患者外周血所有淋巴细胞亚群(T细胞、B细胞、NK细胞)均显著减少。这些发现与呼吸道病毒感染的免疫特征一致,即外周淋巴细胞(尤其是T细胞)在疾病早期迁移至呼吸道,恢复后循环至外周血。外周血活化CD8(+)T细胞计数与疾病严重程度呈负相关,可作为重症流感的预后指标。

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