Sebastian Ricketts

Rank

Undergrad

Department

Medicine

Infectious Disease

Authors

Nicholas Logan, Sebastian Ricketts*, Kathryn Bowman

Principal Investigator

Sarah Fortune

Twitter / Website

Categories

HIV-associated modulation of TB-specific antibody signatures in HIV/TB co-infection

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Abstract

Mycobacterium tuberculosis (Mtb) poses one of the greatest public health concerns globally. HIV-1 is one of the most important risk factors for developing active tuberculosis (TB) and increases the risk of TB reactivation for patients with latent TB (LTBI). Multiple studies point to a role for the humoral immune response in defining disease states in TB, and a potential role in Mtb control. However, recent work suggests alterations to the antibody response during HIV/TB co-infection which differ from the immune profile in TB mono-infection.
Here we aimed to further explore the different antibody fingerprints present within HIV+ and HIV- patients with either latent TB (LTB) or active TB (ATB). We utilized a multiplexed Luminex-based platform to profile Mtb-specific antibody titers across IgM, IgA, and IgG subclasses, Fc receptor (FcR) binding, Fc sialylation and galactosylation, and modifications of innate effector cell response. In this study, plasma samples from 107 individuals were separated by HIV status, TB sputum culture status, and Mantoux skin test results. Univariate analysis demonstrated significant shifts in Mtb-specific subclasses, FcR binding and glycosylation between HIV+ and HIV- groups, with unique antigen-specific differences noted in ATB groups compared with LTBI groups. Within individuals with ATB, there was a notable enrichment in IgG3 in HIV+ individuals. We note decreased FcR2A activity in HIV+ groups, with significantly diminished FcR2A binding in HIV+ individuals with LTBI, compared with HIV- individuals with LTBI, while minimal differences in FcR2A activity were noted across HIV status in the ATB group. This data suggests a HIV-mediated shift in Mtb-specific antibody levels and Fc-mediated binding, with potential implications for associated immune effector functions, including neutrophil and monocyte phagocytosis. These findings provide additional support to understanding the role the humoral system plays during TB infection, particularly within HIV/TB co-infection.