Abstract:

The diagnosis and therapeutic monitoring of tuberculosis still face several critical challenges, including difficulties in etiological sampling for paucibacillary and pediatric cases, inadequate differentiation between active tuberculosis and latent tuberculosis infection, and the absence of reproducible molecular biomarkers for dynamic therapeutic response assessment. In recent years, cell-free RNA (cfRNA), a liquid biopsy signature reflecting host immune responses and transcriptional regulatory profiles, has demonstrated promising application potential in stratified diagnosis and longitudinal monitoring of tuberculosis. Nevertheless, direct clinical evidence supporting cfRNA for tuberculosis infection remains limited, mainly manifested as insufficient sample sizes, overestimated diagnostic performance arising from case-control study designs, lack of independent external validation, and the absence of evaluations on real-world clinical benefits. Centered on core clinical tasks in tuberculosis management, this review summarizes research advances of cfRNA in the identification of active tuberculosis, risk stratification of latent tuberculosis infection, therapeutic response evaluation, and auxiliary diagnosis among special populations. It also generalizes the impacts of key technical procedures—including pre-analytical processing, depletion of highly abundant RNA, library construction and sequencing, targeted quantification, as well as model development and validation—on result stability and clinical translatability. Furthermore, this paper discusses its complementary role alongside existing etiological tests, immunological assays and radiological assessments.

Key words: Tuberculosis, RNA, Diagnosis, differential, Biological markers, Review