Clinical Recovery in Tuberculosis is Associated With the Functional Remodelling of Ag85A-Specific Antibody Avidity and Phagocytic Activity.

Abstract

Tuberculosis (TB) remains a critical global health threat. While research has historically prioritized T-cell immunity, antibodies against highly immunogenic candidates like the Mtb antigen Ag85A are increasingly recognized for their protective roles via Fcγ receptor-mediated effector functions. This study characterized the longitudinal dynamics of B-cells and phagocyte populations alongside Mtb-specific antibody features during TB treatment. A cohort of 20 patients with active TB was followed prospectively for 6 months, with peripheral blood samples collected at baseline (T0), at two (T2) and 6 months (T6) of therapy. The frequencies of circulating immune cells were analysed by flow cytometry, while Ag85A-specific avidity and phagocytic activity were evaluated in patient plasma. Our findings demonstrate a significant, coordinated shift in the host immune profile during anti-TB therapy. We observed a progressive increase in Mtb-specific phagocytic activity and antibody avidity after treatment completion, indicating a functional remodelling of the immune response. Specifically, Ag85A-specific IgG1 levels correlated with phagocytic activity, suggesting it acts as a primary mediator of this effector response. Concurrently, maturation of antibody avidity correlated negatively with bacillary burden. As bacterial load, quantified by sputum smear test (SST), diminished, we noted a concomitant declining trend in circulating CD14+ monocyte and CD66+ granulocytes, indicating a gradual resolution of the inflammatory response. Strikingly, this contraction of the myeloid compartment inversely mirrored a progressive rise in circulating B cell frequencies. This integrated framework outperforms conventional metrics, providing a multi-parametric fingerprint that would be used to track treatment responses and design the next generation of TB immunotherapy.