Targeted Plasma Proteomics of Tuberculosis Patients

Tuberculosis (TB) recurrence following treatment remains poorly understood at the host biological level. Using untargeted mass spectrometry-based plasma proteomics, we conducted the first systematic longitudinal investigation of paired pre- and post-treatment plasma proteomes in culture-confirmed TB recurrence and sustained cure patients within the RePORT India cohort. Recurrence-trajectory patients harboured a distinct immunothrombotic and metabolic signature at diagnosis, characterised by broad complement-coagulation activation and Warburg-like metabolic reprogramming of host immune cells. While sustained cure patients engaged coordinated regulatory rebalancing of these pathways during treatment, recurrence-trajectory patients conspicuously failed to mount this counter-regulatory response. Cortisol-binding globulin and prolactin-induced protein emerged as persistent discriminators across both timepoints, reflecting an unresolved inflammatory state that survives standard therapy. These findings identify host immunothrombotic dysregulation and failed regulatory resolution as potential determinants of recurrence risk, and highlight important proteins for risk stratification in TB-endemic populations.