Diagnostic performance of a cytokine and IFN-γ-induced chemokine mRNA assay after mycobacterium tuberculosis-specific antigen stimulation in whole blood from infected individuals

Sunghyun Kim, Hyejon Lee, Hyunjung Kim, Yeun Kim, Jang Eun Cho, Hyunwoo Jin, Dae Yeon Kim, Sang-Jun Ha, youngae kang, Sangnae Cho, Hyeyoung Lee

Research output: Contribution to journalArticle

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Abstract

Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and evaluated the assay with three different study groups. Results showed that the sensitivity of TNF-α, IL-2R, and CXCL10 in the active pulmonary tuberculosis (PTB) group was 96.43%, 96.43%, and 100%, respectively. The sensitivity of IL-2R and CXCL10 in the latent tuberculosis infection group was 86.36% and 81.82%, respectively. Statistical results showed that TNF-α and CXCL9 were the best individual markers for differentiating between the PTB, LTBI, and non-TB groups. For optimal sensitivity and differentiation of M. tuberculosis infection status, the simultaneous detection of multiple targets was attempted. The combination of IFN-γ, TNF-α, and IL-2R, and the combination of TNF-α, IL-2R, CXCL9, and CXCL10 showed the best performance for detecting active PTB (both 100% positivity) and LTBI (86.36% and 81.82% positivity, respectively). These results imply that the combination of suitable markers is useful in efficiently diagnosing TB and differentiating M. tuberculosis infection status.

Original languageEnglish
Pages (from-to)90-99
Number of pages10
JournalJournal of Molecular Diagnostics
Volume17
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

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Chemokines
Mycobacterium Infections
Interferons
Mycobacterium tuberculosis
Tumor Necrosis Factor-alpha
Cytokines
Messenger RNA
Pulmonary Tuberculosis
Latent Tuberculosis
Tuberculosis
Infection
Interleukin-4
Interleukin-10
Real-Time Polymerase Chain Reaction
Mycobacterium tuberculosis antigens

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

@article{d84329a80b984bc3b3de5520fbb24964,
title = "Diagnostic performance of a cytokine and IFN-γ-induced chemokine mRNA assay after mycobacterium tuberculosis-specific antigen stimulation in whole blood from infected individuals",
abstract = "Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and evaluated the assay with three different study groups. Results showed that the sensitivity of TNF-α, IL-2R, and CXCL10 in the active pulmonary tuberculosis (PTB) group was 96.43{\%}, 96.43{\%}, and 100{\%}, respectively. The sensitivity of IL-2R and CXCL10 in the latent tuberculosis infection group was 86.36{\%} and 81.82{\%}, respectively. Statistical results showed that TNF-α and CXCL9 were the best individual markers for differentiating between the PTB, LTBI, and non-TB groups. For optimal sensitivity and differentiation of M. tuberculosis infection status, the simultaneous detection of multiple targets was attempted. The combination of IFN-γ, TNF-α, and IL-2R, and the combination of TNF-α, IL-2R, CXCL9, and CXCL10 showed the best performance for detecting active PTB (both 100{\%} positivity) and LTBI (86.36{\%} and 81.82{\%} positivity, respectively). These results imply that the combination of suitable markers is useful in efficiently diagnosing TB and differentiating M. tuberculosis infection status.",
author = "Sunghyun Kim and Hyejon Lee and Hyunjung Kim and Yeun Kim and Cho, {Jang Eun} and Hyunwoo Jin and Kim, {Dae Yeon} and Sang-Jun Ha and youngae kang and Sangnae Cho and Hyeyoung Lee",
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Diagnostic performance of a cytokine and IFN-γ-induced chemokine mRNA assay after mycobacterium tuberculosis-specific antigen stimulation in whole blood from infected individuals. / Kim, Sunghyun; Lee, Hyejon; Kim, Hyunjung; Kim, Yeun; Cho, Jang Eun; Jin, Hyunwoo; Kim, Dae Yeon; Ha, Sang-Jun; kang, youngae; Cho, Sangnae; Lee, Hyeyoung.

In: Journal of Molecular Diagnostics, Vol. 17, No. 1, 01.01.2015, p. 90-99.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Kim, Sunghyun

AU - Lee, Hyejon

AU - Kim, Hyunjung

AU - Kim, Yeun

AU - Cho, Jang Eun

AU - Jin, Hyunwoo

AU - Kim, Dae Yeon

AU - Ha, Sang-Jun

AU - kang, youngae

AU - Cho, Sangnae

AU - Lee, Hyeyoung

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N2 - Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and evaluated the assay with three different study groups. Results showed that the sensitivity of TNF-α, IL-2R, and CXCL10 in the active pulmonary tuberculosis (PTB) group was 96.43%, 96.43%, and 100%, respectively. The sensitivity of IL-2R and CXCL10 in the latent tuberculosis infection group was 86.36% and 81.82%, respectively. Statistical results showed that TNF-α and CXCL9 were the best individual markers for differentiating between the PTB, LTBI, and non-TB groups. For optimal sensitivity and differentiation of M. tuberculosis infection status, the simultaneous detection of multiple targets was attempted. The combination of IFN-γ, TNF-α, and IL-2R, and the combination of TNF-α, IL-2R, CXCL9, and CXCL10 showed the best performance for detecting active PTB (both 100% positivity) and LTBI (86.36% and 81.82% positivity, respectively). These results imply that the combination of suitable markers is useful in efficiently diagnosing TB and differentiating M. tuberculosis infection status.

AB - Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and evaluated the assay with three different study groups. Results showed that the sensitivity of TNF-α, IL-2R, and CXCL10 in the active pulmonary tuberculosis (PTB) group was 96.43%, 96.43%, and 100%, respectively. The sensitivity of IL-2R and CXCL10 in the latent tuberculosis infection group was 86.36% and 81.82%, respectively. Statistical results showed that TNF-α and CXCL9 were the best individual markers for differentiating between the PTB, LTBI, and non-TB groups. For optimal sensitivity and differentiation of M. tuberculosis infection status, the simultaneous detection of multiple targets was attempted. The combination of IFN-γ, TNF-α, and IL-2R, and the combination of TNF-α, IL-2R, CXCL9, and CXCL10 showed the best performance for detecting active PTB (both 100% positivity) and LTBI (86.36% and 81.82% positivity, respectively). These results imply that the combination of suitable markers is useful in efficiently diagnosing TB and differentiating M. tuberculosis infection status.

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