Adjunctive biomarkers for improving diagnosis of tuberculosis and monitoring therapeutic effects

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

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / therapeutic use
  • Biomarkers / blood*
  • Chemokine CXCL10 / blood
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunologic Tests
  • Interferon-gamma / blood
  • Interleukin-2
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / drug therapy*
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / diagnosis*
  • Reagent Kits, Diagnostic
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / therapy*
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factor A / blood*
  • Young Adult

Substances

  • Antitubercular Agents
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Cytokines
  • Interleukin-2
  • Reagent Kits, Diagnostic
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interferon-gamma