Serum proteomic analysis of Mycobacterium tuberculosis antigens for discriminating active tuberculosis from latent infection

OBJECTIVE: Serum proteomic analysis of tuberculosis (TB) antigens to identify biomarkers enabling discrimination of active TB (ATB) from latent TB infection (LTBI). METHODS: Serum samples from patients with ATB, individuals with LTBI and healthy controls (HCs) were used to probe proteome microarrays. Based on signal intensities of IgG and IgM antibodies, 100 TB proteins were selected for fabrication of mini-protein microarrays, which were then used to screen 204 serum samples. RESULTS: Proteome microarray analyses showed that 58 IgG or IgM specific antibodies were significantly more abundant in ATB patients than in individuals with LTBI or HCs. Serological evaluation of mini-protein microarrays demonstrated that average levels of 15 specific antibodies were higher in ATB patients than in individuals with LTBI or HCs. This combination of 15 TB serum biomarkers had a sensitivity of 85.4% and specificity of 90.3% in discriminating ATB from LTBI. CONCLUSION: Combinations of serum biomarkers can offer improved diagnostic performance in discriminating ATB from LTBI. Five biomarkers (MT1560.1, Rv0049, Rv0270, Rv1597 and Rv3480c) associated with ATB induced stronger IgM responses in these patients.