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.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Republic of Korea; Institute for Life Science and Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyejon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Republic of Korea.
authors.forename: Yeun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Daegu Health College, Daegu, Republic of Korea.
authors.forename: Jang-Eun
authors.initials: JE
authors.lastname: Cho
authors.affiliation: Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, Republic of Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Internal Medicine, Mokpo National Hospital, Mokpo, Republic of Korea.
authors.forename: Dae Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: raycho@yuhs.ac.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Republic of Korea. Electronic address: hyelee@yonsei.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics* / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma