Activation Phenotype of Mycobacterium tuberculosis-Specific CD4(+) T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection
单位：[1]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,华中科技大学同济医学院附属同济医院检验科[2]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background Rapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue. Methods Participants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4(+) T cells defined by IFN-gamma, TNF-alpha, and IL-2 expression upon MTB antigen stimulation. Results A total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-gamma, TNF-alpha, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-alpha(+) or IL-2(+) cells had superiority over that on IFN-gamma(+) cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-alpha+IL-2(+) cells produced an AUC of 0.901 (95% CI, 0.833-0.969), with a sensitivity of 93.75% (95% CI, 79.85-98.27%) and specificity of 72.97% (95% CI, 57.02-84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-alpha+IL-2(+) cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19-97.47%) sensitivity and 68.97% (95% CI, 50.77-82.73%) specificity. Conclusions We demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.
基金：
Graduate Innovation Fund of
Huazhong University of Science and Technology (grant
number 2021yjsCXCY088) and Special Foundation for
National Science and Technology Basic Research Program of
China (grant number 2019FY101206).
第一作者单位：[1]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,
通讯作者：
推荐引用方式(GB/T 7714)：
luo ying,xue ying,mao liyan,et al.Activation Phenotype of Mycobacterium tuberculosis-Specific CD4(+) T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection[J].FRONTIERS IN IMMUNOLOGY.2021,12:doi:10.3389/fimmu.2021.721013.
APA：
luo,ying,xue,ying,mao,liyan,lin,qun,tang,guoxing...&sun,ziyong.(2021).Activation Phenotype of Mycobacterium tuberculosis-Specific CD4(+) T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection.FRONTIERS IN IMMUNOLOGY,12,
MLA：
luo,ying,et al."Activation Phenotype of Mycobacterium tuberculosis-Specific CD4(+) T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection".FRONTIERS IN IMMUNOLOGY 12.(2021)
医学