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.
Bibliographical noteFunding Information:
We thank the study participants who contributed to this work and we appreciate the staff at Severance Hospital in Seoul, South Korea for their assistance. This study was financially supported by the Ministry for Health, Welfare, and Family Affairs, Republic of Korea (Korean Health Technology R&D Project: A101750 ) and the National Research Foundation of Korea ( 2011-0013018 ). The funding sources had no role in the study process including the design, sample collection, analysis, and interpretation of the results.
All Science Journal Classification (ASJC) codes
- Microbiology (medical)
- Infectious Diseases