title: Discrimination between active and latent tuberculosis based on ratio of antigen-specific to mitogen-induced IP-10 production.
abstract: Mycobacterium tuberculosis is the major causative agent of tuberculosis (TB). The gamma interferon (IFN-γ) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-α), IFN-γ, monokine induced by IFN-γ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. The Mycobacterium tuberculosis antigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-α, IFN-γ, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production to Mycobacterium tuberculosis antigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Jeong
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yun-Gyoung
authors.initials: YG
authors.lastname: Hur
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, Gangwon, Republic of Korea.
authors.forename: Sunghyun
authors.initials: S
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: Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Woman's University, Seoul, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon, Republic of Korea.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Lee
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.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea sjha@yonsei.ac.kr.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D008934:Mitogens