Identification of an eight-protein biosignature for the diagnosis of tuberculosis

Mycobacterium tuberculosis (Mtb) antigen-specific cellular response is promising for detectionof Mtb infection, but not efficient for diagnosis of TB. We firstly identified 16 TB disease-specific protein markers measured in the culture supernatant of Mtb-stimulated whole blood using a 640 human proteins array, the highest throughput antibody-based protein array available at the time when we did this study. Potential TB-related proteins were then analyzed across three different patient cohorts comprised of healthy controls, LTBI, non-TB pneumonia, and TB patients to evaluate how the biomarkers performed in diagnosing TB in the real clinical setting. The data finally reveal an eight-protein biosignature of TB. We prospectively enrolled three cohorts into for our study, including 160 subjects to screen protein biomarkers of tuberculosis, 368 subjects to establish and test the predictive model, and 102 subjects for biomarker validation. Whole blood cultures were stimulated with pooled Mtb-peptides or mitogen, and then 640 proteins within the culture supernatant were analyzed simultaneously using an antibody-based array. 16 candidate biomarkers of tuberculosis were identified and developed into a custom multiplexed antibody array for biomarker validation.