ESAT-6-specific antibody features and Fcγ receptor expression during pulmonary tuberculosis treatment: Implications for therapeutic monitoring

Tuberculosis (TB) remains a leading cause of global mortality, yet the long-term dynamics of antibody-mediated immunity during successful treatment are not fully understood. This study aimed to characterize how ESAT-6-specific antibody profiles, Fc gamma receptor (FcγR) expression, and antibody effector functions change in pulmonary TB patients undergoing treatment. In this exploratory longitudinal study, 21 adults with active pulmonary TB, who completed standard six-month therapy and achieved microbiological cure, were sampled at three time points: before treatment, after two months, and at treatment completion. We quantified ESAT-6-specific immunoglobulin G (IgG) and its subclasses using enzyme-linked immunosorbent assay (ELISA). FcγR expression was assessed via flow cytometry, and antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) were evaluated with cell-based assays. Upon treatment completion, ESAT-6-specific total IgG and IgG4 significantly decreased from baseline in 85.7% and 81.0% of participants, respectively (both q < 0.001). Conversely, ADCP and ADCC increased in 76.2% of participants (q = 0.0017 and q = 0.0014, respectively). Activating FcγR expression also declined, most consistently for CD64 on granulocytes and monocytes, with additional reductions in CD16 and CD32 on monocytes. These findings reveal a coordinated remodeling of ESAT-6-specific humoral immunity during successful TB treatment. We identify IgG4 levels, FcγR expression, ADCP, and ADCC as potential correlates of treatment response. Further validation in larger prospective cohorts, including patients experiencing treatment failure and relapse, is necessary.