Humoral signatures of TB exposure are altered in HIV co-infection

HIV-1 coinfection is an important risk factor for active tuberculosis and increases risk of TB reactivation for individuals with latent TB. Recent work demonstrated that Mtb-specific antibodies can define states of Mtb exposure and disease. However, the performance of Mtb-specific antibody signatures in HIV+ individuals is unclear. We evaluated humoral signatures to a range of Mtb-specific antigens in a South African cohort, consisting of 64 HIV-negative and 51 HIV-positive individuals after IFNγ-release assay using QuantiFERON-Gold plus (QFT). We utilized a Luminex-based platform for humoral profiling of antibodies targeting Mtb antigens, including isotype, subclass, Fc gamma receptor binding, and Fc glycosylation. We compared signatures in individuals with/without positive QFT, and with/without HIV coinfection. Univariate and multivariate analyses showed HIV coinfection modulates Mtb-specific signatures more strongly than QFT status. Although CD4 count and viral load correlated weakly with antibody titers, antibody titers to different Mtb antigens correlated differentially across HIV status. This work demonstrates exposed individuals can produce Mtb-specific antibodies without clinically diagnosed LTBI, and unique patterns of Mtb-specific antigen targeting are seen in HIV/TB coinfection. This work highlights the importance of defining the humoral response in HIV/TB coinfected populations, where diagnostic and prognostic humoral biomarkers may differ from an HIV- population.HIV co-infection with tuberculosis (TB) is a major risk factor for developing active tuberculosis, and increases the risk for developing reactivation of latent TB infection. We evaluated a wide range of different antibodies specific for Mycobacterium tuberculosis (Mtb) in a cohort of South African individuals who were either HIV+ or HIV-, and who had tested positive or negative for latent tuberculosis with a Quantiferon-Gold plus test (QFT). We found that HIV status more strongly influenced the pattern of Mtb-specific antibodies than the QFT testing, and that the characteristics of the Mtb-specific antibodies seen in HIV+ individuals varied significantly from that in HIV- individuals. This data suggests HIV status may significantly shift the fingerprint of antibodies we see in TB disease. Differences in the antibody signature across HIV status highlights an important consideration in the development and use of diagnostic and prognostic biomarkers for tuberculosis.