For analysis of all analytes where available, a seven-marker biosignature comprising unstimulated levels of IFN-γ, IFN-α2, sCD40L, IL-1α, MMP-2, MMP-9 and antigen-specific IFN-α2 diagnosed TB disease with a sensitivity of 81.2% (95% CI 66.9–90.6%) and specificity of 81.2% (95% CI, 70.9–88.5%) in the training sample set (n = 133; n = 48 TB, n = 85 ORD), and a sensitivity of 50.0% (95% CI 27.9–72.1%), and specificity of 83.3% (95% CI 66.5–93.0%) in the test set (n = 56; n = 20 TB and n = 36 ORD). Here, MMP9 is linked to tuberculosis.