An Fc receptor and IgA functional signature identifies TB disease in children living with HIV

Tuberculosis (TB) is a leading cause of morbidity and mortality among children living with HIV (CLHIV). Poor diagnostic performance is a significant contributor. Serological assays that determine levels of Mycobacterium tuberculosis reactive antibodies inconsistently detect TB. However, antigen-specific antibody Fc receptor engagement and effector functions are promising biomarkers of TB disease.

This study evaluated serum from a well-characterized cohort of Kenyan CLHIV via two orthogonal approaches: 1) longitudinally following over the course of TB treatment and 2) assessing a cross-section with and without clinical TB disease. For each individual sample, 13 antibody functional properties against 8 Mtb and 4 non-Mtb microbial antigens were measured and analyzed via univariate and multivariate machine-learning approaches.

FcαR/CD89 immune complex formation with antibodies reactive to four Mtb antigens including ESAT-6 & CFP-10, FcγRI/CD64 associated with one Mtb antigen, and HIV gp120 IgA1 levels decreased during the intensive and continuation/consolidation phases of TB therapy. This antibody signature also highlighted treatment non-responsiveness and distinguished children with from those without TB disease with predictive capacity similar to Xpert.

An Mtb and HIV reactive peripheral blood antibody functional signature of FcαR/CD89, FcγRI/CD64, and IgA1 has the potential to complement current clinical tools and those in development to diagnose pulmonary TB disease in CLHIV.