RISK6 as a Translational Host Transcriptomic Signature for Tuberculosis Diagnosis, Treatment Monitoring, and Risk Stratification

Tuberculosis (TB) remains a leading cause of infectious mortality worldwide, reflecting persistent gaps in diagnosis, risk stratification, and treatment monitoring. Host RNA transcriptomic signatures have emerged as promising tools for capturing dynamic im-mune responses across the TB disease spectrum. Among these, the six-gene RISK6 signa-ture has attracted attention due to its parsimonious design and potential for clinical translation. This review provides a clinically oriented synthesis of current evidence on host transcriptomic biomarkers, with a particular focus on the application of RISK6 in di-agnosis, prediction of disease progression, and treatment monitoring. Available data suggest that RISK6 demonstrates robust diagnostic performance and reliable short-term prognostic value, while also reflecting dynamic changes during therapy. However, varia-bility across populations and the limited evidence in multidrug-resistant TB remain im-portant constraints. In practice, RISK6 is unlikely to function optimally as a standalone biomarker. Its clinical value appears greater when interpreted within integrated frame-works that combine transcriptomic, microbiological, and clinical data. Further validation in diverse populations and real-world settings will be essential to support meaningful clinical implementation.