TY - JOUR
T1 - Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Identifies Diagnostic Biomarkers That Distinguish Active and Latent Tuberculosis
AU - Wang, Sen
AU - He, Lei
AU - Wu, Jing
AU - Zhou, Zumo
AU - Gao, Yan
AU - Chen, Jiazhen
AU - Shao, Lingyun
AU - Zhang, Ying
AU - Zhang, Wenhong
N1 - Funding Information:
This research was funded by the National Science and Technology Major Project of China (2017ZX10201302-004), National Natural Science Foundation of China (81671553 and 81974311), and Shanghai Pujiang Program (2019PJD026).
Publisher Copyright:
© Copyright © 2019 Wang, He, Wu, Zhou, Gao, Chen, Shao, Zhang and Zhang.
PY - 2019/12/18
Y1 - 2019/12/18
N2 - Mycobacterium tuberculosis (M. tuberculosis) infection in humans can cause active disease or latent infection. However, the factors contributing to the maintenance of latent infection vs. disease progression are poorly understood. In this study, we used a genome-wide RNA sequencing (RNA-seq) approach to identify host factors associated with M. tuberculosis infection status and a novel gene signature that can distinguish active disease from latent infection. By RNA-seq, we characterized transcriptional differences in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cells (PBMCs) among three groups: patients with active tuberculosis (ATB), individuals with latent TB infection (LTBI), and TB-uninfected controls (CON). A total of 401 differentially expressed genes enabled grouping of individuals into three clusters. A validation study by quantitative real-time PCR (qRT-PCR) confirmed the differential expression of TNFRSF10C, IFNG, PGM5, EBF3, and A2ML1 between the ATB and LTBI groups. Additional clinical validation was performed to evaluate the diagnostic performance of these five biomarkers using 130 subjects. The 3-gene signature set of TNFRSF10C, EBF3, and A2ML1 enabled correct classification of 91.5% of individuals, with a high sensitivity of 86.2% and specificity of 94.9%. Diagnostic performance of the 3-gene signature set was validated using a clinical cohort of 147 subjects with suspected ATB. The sensitivity and specificity of the 3-gene set for ATB were 82.4 and 92.4%, respectively. In conclusion, we detected distinct gene expression patterns in PBMCs stimulated by PPD depending on the status of M. tuberculosis infection. Furthermore, we identified a 3-gene signature set that could distinguish ATB from LTBI, which may facilitate rapid diagnosis and treatment for more effective disease control.
AB - Mycobacterium tuberculosis (M. tuberculosis) infection in humans can cause active disease or latent infection. However, the factors contributing to the maintenance of latent infection vs. disease progression are poorly understood. In this study, we used a genome-wide RNA sequencing (RNA-seq) approach to identify host factors associated with M. tuberculosis infection status and a novel gene signature that can distinguish active disease from latent infection. By RNA-seq, we characterized transcriptional differences in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cells (PBMCs) among three groups: patients with active tuberculosis (ATB), individuals with latent TB infection (LTBI), and TB-uninfected controls (CON). A total of 401 differentially expressed genes enabled grouping of individuals into three clusters. A validation study by quantitative real-time PCR (qRT-PCR) confirmed the differential expression of TNFRSF10C, IFNG, PGM5, EBF3, and A2ML1 between the ATB and LTBI groups. Additional clinical validation was performed to evaluate the diagnostic performance of these five biomarkers using 130 subjects. The 3-gene signature set of TNFRSF10C, EBF3, and A2ML1 enabled correct classification of 91.5% of individuals, with a high sensitivity of 86.2% and specificity of 94.9%. Diagnostic performance of the 3-gene signature set was validated using a clinical cohort of 147 subjects with suspected ATB. The sensitivity and specificity of the 3-gene set for ATB were 82.4 and 92.4%, respectively. In conclusion, we detected distinct gene expression patterns in PBMCs stimulated by PPD depending on the status of M. tuberculosis infection. Furthermore, we identified a 3-gene signature set that could distinguish ATB from LTBI, which may facilitate rapid diagnosis and treatment for more effective disease control.
KW - RNA sequence
KW - TNFRSF10C
KW - biomarker
KW - latent tuberculosis infection
KW - peripheral blood mononuclear cell
KW - tuberculosis
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U2 - 10.3389/fimmu.2019.02948
DO - 10.3389/fimmu.2019.02948
M3 - Article
C2 - 31921195
AN - SCOPUS:85077332709
SN - 1664-3224
VL - 10
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 2948
ER -