Systemic Host Proteomic Signatures as Dynamic Markers for Monitoring Pulmonary Tuberculosis Treatment Response

Monitoring treatment response of tuberculosis (TB) remains challenging due to the low sensitivity and delayed culture results. Host-derived proteomic biomarker offer a promising alternative by reflecting systemic immune and inflammatory response during therapy. This review aims to systematically evaluate protein-based host biomarkers for monitoring TB treatment response. A systematic search of PubMed and Scopus was conducted for studies published up to September 2025. Eligible studies included human research evaluating protein biomarkers associated with treatment response in adult pulmonary TB. A total of 54 studies comprising 105 distinct biomarkers were included. Biomarkers were grouped into seven categories: acute-phase proteins, inflammatory cytokines, innate immune markers, matrix remodeling enzymes, immune checkpoint molecules, angiogenic factors, and metabolic recovery proteins. Successful treatment was associated with a rapid decline in inflammatory markers followed by modulation of immune and tissue remodeling pathways, while markers of metabolic recovery increased over time. Multi-protein biosignatures demonstrated superior diagnostic performance compared to individual biomarkers. Host-derived proteomic biomarkers provide a dynamic and multidimensional approach to monitoring TB treatment response. While multi-marker signatures show strong potential for clinical application, further standardization, validation, and large-scale studies are required to facilitate their integration into routine TB management.