Specific Cytokines Analysis Incorporating Latency-Associated Antigens Differentiates <i>Mycobacterium tuberculosis</i> Infection Status: An Exploratory Study

Introduction Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states. Methods ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation. Results Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p Esat-6 , IP-10 CFP-10 , IFN-γ Rv1733cSLP , IFN-γ Rv2028c , IL-6 Esat-6 , IL-6 Rv1733cSLP , IL-6 Rv2028c , IL-2 Rv1733cSLP , IL-2 Rv2028c , IL-1Ra Esat-6 , IL-1Ra CFP-10 , IL-1Ra Rv2028c , CXCL-1 Esat-6 , CXCL-1 CFP-10 , CXCL-1 Rv1733cSLP , CXCL-1 Rv2028c , MCP-1 Esat-6 and MCP-1 CFP-10 , demonstrated accurate discrimination between ATB and LTBI ( p p =0.038), IFN-γ increased from 0.806 to 0.962 ( p =0.025), and IL-2 increased from 0.565 to 0.868 ( p =0.007). Model selected by forward likelihood method indicated combined detection of IFN-γ CFP-10 , IFN-γ Rv1733cSLP , IP-10 Rv1733cSLP , and CXCL-1 Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γ CFP-10 and IFN-γ Rv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943). Conclusion Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.