Mycobacterium tuberculosis Secreted Proteins As Potential Biomarkers for the Diagnosis of Active Tuberculosis and Latent Tuberculosis Infection

BACKGROUND: The detection of Mycobacterium tuberculosis (Mtb) specific human antibodies has been an important diagnostic aid in the diagnosis of tuberculosis (TB) cases with smear‐negative sputum samples, especially for the screening of high‐risk population. This study focused on the analysis and comparison of the four potential Mtb‐secreted proteins (ESAT6, CFP10, Ag85B, Hsp16.3) and the fusion protein Ag85B‐Hsp16.3 as new markers in the serodiagnosis between active TB and latent TB infection (LTBI). METHODS: These five recombinant proteins were produced and used in optimized ELISA to detect IgG serum antibodies against the four secreted proteins. The capacity of identifying infection was evaluated either in active TB patients or LTBI individuals, which was compared with the control groups consisting of hospitalized non‐TB individuals. RESULTS: The results showed that Ag85B‐Hsp16.3/ESAT6 and Hsp16.3/ESAT6 were the best‐associated antigens for serology diagnosis of the active TB and LTBI individuals because of their specificity, sensitivity, YI values, and positive rates, respectively. ELISA test demonstrated that 41.67% (25/60) of blood donors respond to Ag85B‐Hsp16.3/ESAT6. The consistency of this positive respond with clinical diagnosis almost reached 84% (21/25). CONCLUSION: Thus, a combined test of multiple Mtb‐secreted proteins Ag85B, Hsp16.3, and ESAT6 may be the ascendant preliminary screening antigens for active TB or LTBI patients.