Tuberculosis treatment and cytotoxic immune signatures: a longitudinal study

Background Tuberculosis (TB) remains a leading cause of global mortality. Current tools for monitoring therapeutic efficacy are suboptimal, creating an urgent need for novel strategies. While emerging evidence suggests that immune biomarkers could fill this gap, our understanding of antibody dynamics during TB treatment remains limited. Beyond neutralization, antibodies play a critical role in the immune response by modulating inflammation and mediating the clearance of infected cells. Methods In a longitudinal cohort of active TB patients, we analyzed Ag85A-specific antibody-dependent cellular cytotoxicity (ADCC) and perforin-expressing NK cells via flow cytometry. Ag85A-specific IgG subclasses were measured by ELISA to correlate humoral architecture with cytotoxic potency. Results The analysis revealed a significant increase in Ag85A-specific antibodies capable of mediating cytotoxic activity, which was associated with elevated levels of NK cells producing perforin upon treatment completion. Furthermore, ADCC activity correlates with Mtb -specific IgG subclasses and treatment time duration. Notably, a longitudinal decline in Ag85A-specific IgG3 levels emerged as a distinct signature of bacterial clearance and clinical resolution, suggesting a transition from acute inflammatory responses toward a resolved immune profile characterized by sustained cytotoxic potential. Conclusions Clinical resolution of TB is characterized by the potentiation of the ADCC-NK cell axis. The reduction in IgG3 levels reflects a shifting inflammatory milieu, while enhanced cellular cytotoxicity serves as a primary immunological hallmark and a potential biomarker for treatment monitoring.