Functional compartmentalization of antibodies in the central nervous system during chronic HIV infection
Name
jiac138.pdf
Description
Published version
Size
1.55 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Spatola, Marianna
Loos, Carolin
Cizmeci, Deniz
Webb, Nicholas
Gorman, Matthew J
Rossignol, Evan
Shin, Sally
Yuan, Dansu
Fontana, Laura
Mukerji, Shibani S
Date Issued
2022
Journal
Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Citation
Spatola, Marianna, Loos, Carolin, Cizmeci, Deniz, Webb, Nicholas, Gorman, Matthew J et al. 2022. "Functional compartmentalization of antibodies in the central nervous system during chronic HIV infection." Journal of Infectious Diseases, 226 (4).
Version
Final published version
Abstract
Abstract
The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating HIV must include CNS-targeted strategies. Given the inaccessibility of the brain, efforts have focused on cerebrospinal fluid (CSF), aimed at defining biomarkers of HIV-disease in the CNS, including HIV-specific antibodies. However, how antibodies traffic between the blood and CNS, and whether specific antibody profiles track with HIV-associated neurocognitive disorders (HAND) remains unclear. Here, we comprehensively profiled HIV-specific antibodies across plasma and CSF from 20 antiretroviral therapy (ART) naive or treated persons with HIV. CSF was populated by IgG1 and IgG3 antibodies, with reduced Fc-effector profiles. While ART improved plasma antibody functional coordination, CSF profiles were unaffected by ART and were unrelated to HAND severity. These data point to a functional sieving of antibodies across the blood-brain barrier, providing previously unappreciated insights for the development of next-generation therapeutics targeting the CNS reservoir.
The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating HIV must include CNS-targeted strategies. Given the inaccessibility of the brain, efforts have focused on cerebrospinal fluid (CSF), aimed at defining biomarkers of HIV-disease in the CNS, including HIV-specific antibodies. However, how antibodies traffic between the blood and CNS, and whether specific antibody profiles track with HIV-associated neurocognitive disorders (HAND) remains unclear. Here, we comprehensively profiled HIV-specific antibodies across plasma and CSF from 20 antiretroviral therapy (ART) naive or treated persons with HIV. CSF was populated by IgG1 and IgG3 antibodies, with reduced Fc-effector profiles. While ART improved plasma antibody functional coordination, CSF profiles were unaffected by ART and were unrelated to HAND severity. These data point to a functional sieving of antibodies across the blood-brain barrier, providing previously unappreciated insights for the development of next-generation therapeutics targeting the CNS reservoir.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1093/INFDIS/JIAC138
