Potential Biomarkers Associated with Discrimination Between Latent and Active Pulmonary Tuberculosis

Setting: A third of the world's population has latent tuberculous infection (LTBI). Current TB diagnostics used in developing countries are ineffective and are unable to distinguish LTBI from active TB. Identifying biomarkers that could aid in the early detection of TB and in distinguishing TB states could be a major breakthrough in global TB control.

Objective: To identify potential immune biomarkers to distinguish active TB from LTBI.

Design: A cross-sectional study was conducted among 19 active TB patients, 8 TB-negative individuals (controls) and 16 LTBI non-human immunodeficiency virus infected individuals in Nairobi, Kenya. Excess supernatants from the QuantiFERON®-TB Gold In-Tube test were used to measure immune analytes using a Th17-focused Milliplex® assay.

Results: Overall antigen-specific responses were higher in the LTBI group than in active TB patients and controls. Interleukin (IL) 17F, macrophage inflammatory protein 3 alpha (MIP-3α), IL-13, IL-17A, IL-5, interferon-gamma (IFN-γ), IL-9, IL-1β and IL-2 were significantly differentially produced by individuals with LTBI and active TB patients. Receiver operator curve analysis revealed good discriminative abilities of these analytes. Co-expression analysis highlighted uniquely co-expressed cytokine pairs between TB groups.

Conclusion: These findings suggest that IL-17F, MIP-3α, IL-13, IL-17A, IL-5, IL-9, IL-1β and IL-2, in addition to IFN-γ, could identify and uniquely discriminate between TB states.