Editorial: Unveiling Distinctions: Active Tuberculosis versus Latent Tuberculosis Infection -Immunological Insights, Biomarkers, and Innovative Approaches

Ying Luo^*

• University of Texas Southwestern Medical Center, Dallas, United States

effective management and control of the disease. Rapid and precise diagnosis of TB not only facilitates timely treatment but also plays a pivotal role in interrupting the transmission of Mycobacterium tuberculosis (MTB). However, the development of sensitive and reliable diagnostic approaches for TB remains a significant unmet need, underscoring the necessity for innovative methods that can be translated into clinical practice.This topic collection aims to attract innovative studies that contribute to the development of a comprehensive diagnostic toolkit enabling clinicians to distinguish ATB from LTBI with heightened precision. In this collection, a total of 11 papers, including 9 original demonstrated by a series of recent reports in this field (2)(3)(4)(5)(6)(7). However, significant 51 limitations in TB diagnostics persist. First, rigorous validation of candidate biomarkers in 52 diverse, well-powered cohorts is essential to facilitate the translation of promising 53 markers from individual laboratories to standardized and commercially viable clinical 54 assays. This underscores the need to establish stringent criteria for selecting 55 candidates with true diagnostic utility. Second, there is a need to facilitate investigations 56 into the immunopathology of TB to enable the dissection of molecular dynamics 57 throughout the disease course. Such mechanistic insights will not only advance our 58 understanding of TB pathogenesis but also inform the development of clinically 59 actionable biomarkers and therapeutic targets. Moreover, improving the quality and 60 reproducibility of clinical testing is imperative to reduce variability arising from 61 uncontrolled data quality, which often complicates interpretation. Researchers should devote attention to investigating the biological underpinnings of outlier data rather than 63 dismissing them as heterogeneity observed in underscores the 64 importance of focusing on individual-level variations rather than solely on cohort-level 65 statistical significance. Rare findings in clinical data may, in fact, reflect meaningful 66 biological phenomena requiring further exploration. Detailed analyses at the individual 67 patient level, alongside cohort-based assessments, will ultimately yield insights that 68 benefit both the broader TB population and individual patients. Finally, it is critical that 69 researchers bridge observations from clinical settings with mechanistic insights from 70 experimental models, fostering a translational pipeline that connects clinical phenomena 71 to biological mechanisms. Such integrative efforts will be pivotal for advancing TB 72 diagnostics and therapeutics in a manner that truly impacts patient care. 73