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Discrimination between active and latent tuberculosis based on ratio of antigen-specific to mitogen-induced IP-10 production

 Yun Hee Jeong  ;  Yun-Gyoung Hur  ;  Hyejon Lee  ;  Sunghyun Kim  ;  Jang-Eun Cho  ;  Jun Chang  ;  Sung Jae Shin  ;  Hyeyoung Lee  ;  Young Ae Kang  ;  Sang-Nae Cho  ;  Sang-Jun Ha 
 JOURNAL OF CLINICAL MICROBIOLOGY, Vol.53(2) : 504-510, 2015 
Journal Title
Issue Date
Adult ; Antigens, Bacterial/immunology* ; Chemokine CXCL10/secretion* ; Diagnosis, Differential ; Female ; Humans ; Interferon-gamma Release Tests/methods* ; Leukocytes, Mononuclear/immunology* ; Male ; Middle Aged ; Mitogens/metabolism* ; Mycobacterium tuberculosis/immunology* ; Tuberculosis/diagnosis* ; Young Adult
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Ae(강영애) ORCID logo https://orcid.org/0000-0002-7783-5271
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Lee, Hyejon(이혜존) ORCID logo https://orcid.org/0000-0001-8207-537X
Cho, Sang Nae(조상래)
Hur, Yun-Gyoung(허윤경) ORCID logo https://orcid.org/0000-0003-3986-4394
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