212例活动性结核病患者外周血淋巴细胞亚群特点:单中心描述性研究

Changes of Peripheral Blood Lymphocyte Subsets in 212 Active Tuberculosis Patients:A Uni-centered Descriptive Study

目的基于相对较大的样本数据,探究活动性结核病(active tuberculosis,ATB)患者外周血淋巴细胞亚群特点及其意义。方法回顾性收集北京协和医院住院ATB患者(2012年6月—2022年1月)及年龄、性别与其相匹配的健康人群(2019年3月—2022年5月)的临床资料。以健康人群为对照,分析ATB患者外周血淋巴细胞亚群变化特点,并对不同确诊方式及受累部位ATB患者进行组间比较。结果共入选符合纳入与排除标准的ATB患者212例、健康人群200例。ATB患者中,临床确诊82例(38.7%)、病原学确诊130例(61.3%,包括单纯肺结核77例、单纯肺外结核21例、肺结核并肺外结核32例)。相较于健康人群,ATB患者多种外周血淋巴细胞亚群指标计数及其百分比降低(P均<0.05),T淋巴细胞百分比、CD8^(+)T淋巴细胞百分比、记忆CD4^(+)T淋巴细胞/CD4^(+)T淋巴细胞比值、CD38^(+)CD8^(+)T淋巴细胞/CD8^(+)T淋巴细胞比值等均升高(P均<0.05)。相较于临床确诊ATB患者,病原学确诊ATB患者淋巴细胞、B细胞、自然杀伤(natural killer,NK)细胞、T淋巴细胞、CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞计数等均降低(P均<0.05)。不同结核感染部位的患者记忆CD4^(+)T淋巴细胞、纯真CD4^(+)T淋巴细胞、CD28^(+)T淋巴细胞及活化CD8^(+)T淋巴细胞亚群计数及其百分比无显著差异(P均>0.05)。相较于单纯肺结核患者,肺结核并肺外结核患者B细胞计数[23(10,69)个/μL比73(25,133)个/μL,P=0.003]降低,单纯肺外结核患者NK细胞百分比[16.7%(10.8%,23.6%)比10.6%(5.3%,17.4%),P=0.042]升高。结论ATB患者外周血淋巴细胞亚群指标整体呈减低状态,存在明显的免疫功能紊乱。

Objective To explore the characteristics and their significance of peripheral blood lymphocyte subsets in patients with active tuberculosis(ATB),based on a relatively large sample.Methods Clinical data were retrospectively collected from patients with ATB hospitalized in Peking Union Medical College Hospital(June 2012-January 2022)and the healthy population matched with age and sex(March 2019-May 2022).The characteristics of changes in peripheral blood lymphocyte subsets in ATB patients were analyzed using the healthy population as controls,and group comparisons were made between ATB patients with different modes of diagnosis and sites of involvement.Results A total of 212 ATB patients and 200 healthy participants were included.ATB patients consisted of 82 cases(38.7%)without etiological evidence and 130 cases(61.3%)with etiological evidence(77 with pulmonary tuberculosis,21 with extrapulmonary tuberculosis,and 32 with pulmonary and extrapulmonary tuberculosis).Compared to healthy population,ATB patients had significantly lower counts and percentages of multiple peripheral blood lymphocyte subsets indicators,significantly higher percentage in T lymphocyte,CD8^(+)T lymphocyte as well as higher memory CD4^(+)T lymphocyte/CD4^(+)T lymphocyte ratio and CD38^(+)CD8^(+)T lymphocyte/CD8^(+)T lymphocyte ratio(all P<0.05).Lymphocyte,B-cell,natural killer(NK)cell,T-lymphocyte,CD4^(+)T-lymphocyte,and CD8^(+)T-lymphocyte counts were lower in patients with pathogenetically confirmed ATB than in those with clinically confirmed ATB(all P<0.05).There were no significant differences in the counts of memory CD4^(+)T lymphocytes,naïve CD4^(+)T lymphocytes,CD28^(+)T lymphocytes and activated CD8^(+)T lymphocyte subpopulations and their percentages in patients with different tuberculosis infection sites(all P>0.05).Compared to pulmonary tuberculosis alone,patients with pulmonary and extrapulmonary tuberculosis had lower B-cell counts[23(10,69)cells/μL vs.73(25,133)cells/μL,P=0.003]and patients with extrapulmonary tuberculosis alone had higher percentages of NK cells[16.7%(10.8%,23.6%)vs.10.6%(5.3%,17.4%),P=0.042].Conclusion ATB patients manifested a reduction in peripheral blood lymphocyte subset,indicating remarkable dysfunction of immune system.