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J Infect. 2015 Apr;70(4):346-55. doi: 10.1016/j.jinf.2014.10.019. Epub 2014 Nov 5.

Adjunctive biomarkers for improving diagnosis of tuberculosis and monitoring therapeutic effects.

Author information

1
Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
2
Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
3
Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: raycho@yuhs.ac.

Abstract

OBJECTIVES:

To identify host biomarkers associated with latent tuberculosis infection (LTBI), active tuberculosis (TB), and nontuberculous mycobacteria (NTM) diseases to improve diagnosis and effective anti-TB treatment.

METHODS:

Active TB and NTM patients at diagnosis, recent TB contacts, and normal healthy subjects were recruited. Tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, and multiplex bead arrays with 17 analytes were performed. TB patients were re-evaluated after 2 and 6 months of treatment.

RESULTS:

Mycobacterium tuberculosis (M. tb) antigen-specific IFN-γ, IL-2, and CXCL10 responses were significantly higher in active TB and LTBI compared with controls (P < 0.01). Only serum VEGF levels varied between the active TB and LTBI groups (AUC = 0.7576, P < 0.001). Active TB and NTM diseases were differentiated by serum IL-2, IL-9, IL-13, IL-17, TNF-α and sCD40L levels (P < 0.05). Increased sCD40L and decreased M. tb antigen-specific IFN-γ levels correlated with sputum clearance of M. tb after 2 months of treatment (P < 0.001).

CONCLUSIONS:

Serum IL-2, IL-9, IL-13, IL-17, TNF-α, sCD40L and VEGF-A levels may be adjunctive biomarkers for differential diagnosis of active TB, LTBI, and NTM disease. Assessment of serum sCD40L and M. tb antigen-specific IFN-γ, TNF-α, and IL-2 levels could help predict successful anti-TB treatment in conjunction with M. tb clearance.

KEYWORDS:

Biomarker; Diagnosis; Latent tuberculosis infection (LTBI); Mycobacterium tuberculosis (M. tb); Nontuberculous mycobacteria (NTM); Treatment; Tuberculosis (TB)

PMID:
25452040
DOI:
10.1016/j.jinf.2014.10.019
[Indexed for MEDLINE]
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