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

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 increasi...

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Autores principales:	Esther van Woudenbergh, Edward B. Irvine, Leela Davies, Marwou de Kock, Willem A. Hanekom, Cheryl L. Day, Sarah Fortune, Galit Alter
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV antibodies coinfection humoral immunity tuberculosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6dd70743b50f4efbacbe65ac9b0888a3
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spelling	oai:doaj.org-article:6dd70743b50f4efbacbe65ac9b0888a32021-11-15T15:30:15ZHIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection10.1128/mSphere.00104-202379-5042https://doaj.org/article/6dd70743b50f4efbacbe65ac9b0888a32020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00104-20https://doaj.org/toc/2379-5042ABSTRACT 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, HIV-positive individuals demonstrating compromised antigen-specific IgM titers. HIV-infected individuals with active TB also exhibited a significant loss of influenza hemagglutinin- and 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. IMPORTANCE TB is the leading cause of death from a single infectious agent globally, followed by HIV. Furthermore, TB represents the leading cause of death among people with HIV. HIV is known to cause severe defects in T cell immunity, rendering HIV/TB-coinfected individuals more susceptible to TB disease progression and complicating accurate TB disease diagnosis. Here, we demonstrate that HIV infection is additionally associated with severely compromised antibody responses, particularly in individuals with active TB. Moreover, despite the influence of HIV infection, antibody profiles still allow accurate classification of individuals with active versus latent TB. These findings reveal novel immunologic challenges associated with HIV/TB coinfection and additionally provide a basis with which to leverage the key antibody features identified to potentially combat TB globally via next-generation therapeutic or diagnostic design.Esther van WoudenberghEdward B. IrvineLeela DaviesMarwou de KockWillem A. HanekomCheryl L. DaySarah FortuneGalit AlterAmerican Society for MicrobiologyarticleHIVantibodiescoinfectionhumoral immunitytuberculosisMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV antibodies coinfection humoral immunity tuberculosis Microbiology QR1-502
spellingShingle	HIV antibodies coinfection humoral immunity tuberculosis Microbiology QR1-502 Esther van Woudenbergh Edward B. Irvine Leela Davies Marwou de Kock Willem A. Hanekom Cheryl L. Day Sarah Fortune Galit Alter HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
description	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, HIV-positive individuals demonstrating compromised antigen-specific IgM titers. HIV-infected individuals with active TB also exhibited a significant loss of influenza hemagglutinin- and 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. IMPORTANCE TB is the leading cause of death from a single infectious agent globally, followed by HIV. Furthermore, TB represents the leading cause of death among people with HIV. HIV is known to cause severe defects in T cell immunity, rendering HIV/TB-coinfected individuals more susceptible to TB disease progression and complicating accurate TB disease diagnosis. Here, we demonstrate that HIV infection is additionally associated with severely compromised antibody responses, particularly in individuals with active TB. Moreover, despite the influence of HIV infection, antibody profiles still allow accurate classification of individuals with active versus latent TB. These findings reveal novel immunologic challenges associated with HIV/TB coinfection and additionally provide a basis with which to leverage the key antibody features identified to potentially combat TB globally via next-generation therapeutic or diagnostic design.
format	article
author	Esther van Woudenbergh Edward B. Irvine Leela Davies Marwou de Kock Willem A. Hanekom Cheryl L. Day Sarah Fortune Galit Alter
author_facet	Esther van Woudenbergh Edward B. Irvine Leela Davies Marwou de Kock Willem A. Hanekom Cheryl L. Day Sarah Fortune Galit Alter
author_sort	Esther van Woudenbergh
title	HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
title_short	HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
title_full	HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
title_fullStr	HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
title_full_unstemmed	HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection
title_sort	hiv is associated with modified humoral immune responses in the setting of hiv/tb coinfection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6dd70743b50f4efbacbe65ac9b0888a3
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HIV Is Associated with Modified Humoral Immune Responses in the Setting of HIV/TB Coinfection

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