Longitudinal Plasma Proteomic Profiling Reveals Divergent Immune Responses in Durably Cured and Relapsed Pulmonary Tuberculosis

Background : Although clinical biomarkers of tuberculosis (TB) relapse are well characterized, the biological mechanisms underlying different treatment outcomes remain poorly understood. Elucidating these mechanisms may reveal improved biomarkers of long-term treatment outcomes. Methods : We conducted a longitudinal, global proteomic study on 60 participants with active pulmonary TB, half who were durably cured and half who relapsed. Plasma was collected at seven time-points: at treatment initiation (baseline), during therapy, and 52 weeks postbaseline. Samples were analyzed by high-resolution LC-MS/MS. Results : 2,418 proteins were identified across all samples, with 1,756 being differentially expressed relative to baseline ( p Conclusions : Heightened humoral and innate immune responses were associated with relapse, whereas recovery signatures were associated with durable cure. Several proteins showed potential as relapse biomarkers and warrant future validation in independent cohorts. These findings advance our understanding of host responses to treatment and provide a basis for developing blood-based biomarkers to identify patients at increased risk of relapse.