The serum biosignature consisting of 16 proteins (APRIL/TNFSF13, sCD30/TNFRSF8, chitinase 3-like 1, sIL-6Rα, IL-8, IL-11, IL-12(p70), IL-19, IL-28A/IFN-λ2, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, OPN, PTX-3, TWEAK/TNFSF12) was found informative for the differentiation between the TB and HC groups, while the panel of 15 proteins (IL-6, APRIL/TNFSF13, sCD30/TNFRSF8, gp130/sIL-6β, IL-2, sIL-6Rα, IL-8, IL-29/IFNλ1, IL-35, MMP-2, MMP-3, OPN, PTX-3, sTNF-R2, TWEAK/TNFSF12) distinguished the HC group from the LTBI cohort. The gene discussed is SPP1; the disease is tuberculosis.