The blood biomarker combination IL-8/IL-33 and IL-18/IL-33 distinguish between active tuberculosis and latent infection.

PURPOSES: A leading cause of death from infectious diseases worldwide is tuberculosis (TB), and it often arises from latent infection. New diagnostic tests for latent tuberculosis infection (LTBI) are needed. Therefore, this study aimed to identify novel biomarker signatures in whole human blood to distinguish between active tuberculosis (ATB) and LTBI.

METHODS: Two LEGENDplexkits were used to evaluate the secretion levels of 20 cytokines triggered by ESAT-6/CFP10 antigen in whole blood of ATB, LTBI, and healthy controls, and to search for cytokine combinations utilized to distinguish between ATB and LTBI.

RESULTS: IL-8, IL-18, IL-33, MCP-1, MIG (baseline levels); IL-8, IL-33, IL-1β, MCP-1, MIG, IL-10, I-TAC (ESAT-6/CFP10-stimulated levels); and IL-18, IL-33, IL-1β, IL-10, TNF-α (ESAT-6/CFP10-stimulated minus baseline levels) had the potential to distinguish ATB from LTBI. Our data shows that the sensitivity and specificity of targeted IL-8 and IL-33 distinguishing between ATB and LTBI were 83.3% and 93.75%, and the diagnostic accuracy was 89.28%, and the sensitivity and specificity of targeted IL-18 and IL-33 distinguishing between ATB and LTBI were 91.67% and 81.25%, with the diagnostic accuracy was 85.71%.

CONCLUSIONS: Our data suggest that IL-8/IL-33 and IL-33/IL-18 together can be utilized as immunological markers to differentiate between LTBI and ATB. A novel TB diagnostic protocol was established, offering novel perspectives to create better tests.