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Identification of novel antigens for distinguishing between active tuberculosis and latent tuberculosis infection in
Haiping Dong1, Bin Huang2, Haobin Kuang3
1Guangzhou Key Laboratory of Tuberculosis Research, Guangzhou Chest Hospital, China; State Key Laboratory of Respiratory Disease, China; Department of Tuberculosis, Guangzhou Chest Hospital, China; Guangzhou Medical University, Guangdong, China.
Introduction:
Tuberculosis (TB) remains a significant global health threat, with latent tuberculosis infection (LTBI) serving as a major reservoir for new TB cases. This study aimed to identify antigens capable of distinguishing between active tuberculosis (ATB) and LTBI in interferon-γ release assays (IGRA).
Methods:
Four candidate antigens for LTBI and two for ATB were selected based on a literature review. These antigens were synthesized genetically, subcloned, expressed in bacteria, and purified. Clinical samples were collected from individuals diagnosed with ATB and LTBI to aid in assay development. Novel IGRA assays were then developed using these antigens, and their discriminatory efficacy was assessed.
Results:
Among the six candidate antigens tested, only three (Rv2028c, Rv2029c and Rv0475) showed promising discriminatory potential for LTBI. Particularly, Rv0475 (HBHA), expressed in Escherichia coli without methylation, exhibited greater stimulation activity in LTBI compared to ATB. Individually, these antigens demonstrated sensitivities ranging from 72.4% to 93.3% and specificities ranging from 79.3% to 89.7%. The combined stimulation of multiple antigens can improve the sensitivity and specificity of the diagnosis.
Conclusion:
Our findings highlight the potential of three LTBI antigens and their combination in distinguishing between ATB and LTBI. Adding this antigen combination to the traditional IGRA assay could significantly improve the clinical differentiation of healthy individuals, LTBI, and ATB. Further investigation in larger and more diverse patient cohorts is warranted to validate the utility of these antigen combinations in clinical settings.
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