Host-response biomarkers for precision tuberculosis: from immune transcriptomic signatures to clinical risk stratification.

Tuberculosis (TB) remains a major infectious cause of morbidity and mortality, while current diagnostic and treatment-monitoring pathways remain largely pathogen-centered. Microbiological tests are indispensable for confirming TB and detecting drug resistance, but they do not directly measure host inflammatory activity, disease-stage heterogeneity, risk of progression, biological response to therapy, or recurrence after treatment completion. Host-response biomarkers, particularly blood transcriptomic signatures, provide a complementary route toward precision TB medicine. Recent multicenter validation studies, household-contact cohorts, treatment-monitoring analyses, cell-free RNA profiling, single-cell studies, and recurrence cohorts have refined the translational evidence base for immune transcriptomic biomarkers. Across studies, active and progressive TB is characterized by interferon-inducible transcription, inflammatory myeloid remodeling, neutrophil and monocyte activation, antigen-specific T-cell activation, and partial normalization during effective therapy. These signals can support clinically relevant use cases, including sputum-independent triage of symptomatic patients, short-term prediction of progression among exposed contacts, identification of subclinical or incipient disease biology, treatment-response monitoring, and post-treatment recurrence detection. However, implementation is constrained by imperfect specificity against non-TB inflammation, heterogeneity across HIV, diabetes, pediatric, extrapulmonary and geographically diverse populations, assay standardization requirements, and limited interventional evidence. This Mini Review synthesizes recent evidence and proposes a focused translational framework linking immune transcriptomic mechanisms to actionable clinical risk stratification in TB.