HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection

• Type of Material: Article
• Authors: Esther van Woudenbergh, Ragon Institute; Edward B. Irvine, Ragon Institute; Leela Davies, Ragon Institute; Marwou de Kock, University of Cape Town; Willem A. Hanekom, University of Cape Town; Cheryl Day, Emory University; Sarah Fortune, Ragon Institute; Galit Alter, Ragon Institute
• Language: English
• Date: 2020-05-01
• Publisher: AMER SOC MICROBIOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 van Woudenbergh et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/mSphere.00104-20
• Title of Journal or Parent Work: MSPHERE
• Volume: 5
• Issue: 3
• Grant/Funding Information: This work was supported by the Ragon Institute and the SAMANA Kay MGH Research Scholar program. We also thank the Nora Baart Foundation, K. F. Hein Foundation, Jo Kolk Study Foundation, Hendrik Muller Foundation, and Utrecht Selective Life Sciences ExtraCurricular Track (U/Select) for financially supporting E.V.W.
• Keywords: ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-TUBERCULOSIS; HIV; HEMOLYSIN-FORMING CELLS; ANTIGEN; tuberculosis; B-CELLS; INFECTION; ANTIBODY-RESPONSES; Science & Technology; coinfection; T-CELLS; antibodies; Microbiology; Life Sciences & Biomedicine; FC-GAMMA RECEPTORS; humoral immunity; HIGH-THROUGHPUT
• Research Categories: Biology, Microbiology; Biology, Virology; Biology, Cell

Abstract

Tuberculosis (TB) represents the largest cause of death in human immunodeficiency virus (HIV)-infected individuals in part due to HIV-related CD4+ T cell loss, rendering patients immunocompromised and susceptible to a loss of Mycobacterium tuberculosis control. However, in light of increasing data pointing to a role for humoral immunity in controlling M. tuberculosis infection, here, we aimed to define whether HIV infection also alters the humoral immune response in subjects with active and latent TB. We show that in the setting of active TB, HIV-positive individuals have significantly lower IgG responses to LAM and Ag85 than HIV-negative individuals. Furthermore, significant isotype/subclass-specific differences were frequently observed, with active TB, HIVpositive individuals demonstrating compromised antigen-specific IgM titers. HIV-infected individuals with active TB also exhibited a significant loss of influenza hemagglutininand tetanus toxoid-specific antibody titers at the isotype/subclass level, a symptom of broad humoral immune dysfunction likely precipitated by HIV infection. Finally, we illustrated that despite the influence of HIV infection, differences in M. tuberculosis-specific antibody profiles persist between latent and active TB disease. Taken together, these findings reveal significant HIV-associated disruptions of the humoral immune response in HIV/TB-coinfected individuals.