Early Mycobacterial Antigens in the Immunodiagnosis of Latent Tuberculosis Infection
Utegenova A. Kassayeva L. Turdalina B. Baiduissenova A. Yktiyarov A. Dusmagambetov M. Sokurenko E.
February 2026Multidisciplinary Digital Publishing Institute (MDPI)
Pathogens
2026#15Issue 2
Latent tuberculosis infection (LTBI) represents a major global health concern as it constitutes the principal reservoir for future tuberculosis (TB) disease. Its identification is particularly important in Bacille Calmette–Guérin (BCG)-vaccinated populations, where cross-reactivity of purified protein derivative limits the specificity of the tuberculin skin test and hampers targeted preventive therapy. Early Mycobacterium tuberculosis antigens encoded within the RD1 region, especially ESAT-6, CFP-10 and TB7.7, have enabled the development of antigen-specific interferon-gamma release assays (IGRAs) and recombinant skin tests with improved BCG-independent specificity. This narrative review integrates and critically appraises current evidence on the immunobiological properties of early and latency-associated antigens, the cellular mechanisms underlying T-cell-dependent immune reactivity, and the diagnostic performance of IGRAs and ESAT-6/CFP-10-based skin tests, rather than merely summarizing individual studies. Although these platforms rely on different assay principles (in vitro cytokine release versus in vivo delayed-type hypersensitivity), both measure antigen-specific T-cell memory and do not define the biological stage of infection or reliably distinguish latent from incipient or active TB. Across most adult populations, IGRAs demonstrate high specificity and acceptable sensitivity, whereas reduced sensitivity and higher rates of indeterminate results are observed in young children and immunocompromised individuals. ESAT-6/CFP-10-based skin tests show diagnostic accuracy comparable to IGRAs and may offer operational advantages in resource-limited settings. Latency-associated antigens and host biomarkers such as IP-10, together with multi-analyte immune signatures, represent promising avenues for improving diagnostic sensitivity and prognostic stratification but currently lack sufficient validation for routine clinical use. Overall, RD1-encoded antigens remain central to LTBI immunodiagnosis, while future research should focus on developing stage-resolving and prognostic biomarkers, optimized antigen panels, and standardized interpretive frameworks.
CFP-10 , DosR antigens , ESAT-6 , interferon-gamma release assay , IP-10 , latent tuberculosis infection , QuantiFERON-TB Gold Plus , T-SPOT.TB
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Department of Microbiology and Virology, Astana Medical University, Astana, 010000, Kazakhstan
Department of Phthisiopulmonology and Radiology, South Kazakhstan Medical Academy, Shymkent, 160019, Kazakhstan
Department of Pediatric Infectious Diseases, Astana Medical University, Astana, 010000, Kazakhstan
Department of Microbiology, School of Medicine, University of Washington, Seattle, 98195, WA, United States
Department of Microbiology and Virology
Department of Phthisiopulmonology and Radiology
Department of Pediatric Infectious Diseases
Department of Microbiology
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