1. Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection.
- Author
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Spatola M, Loos C, Cizmeci D, Webb N, Gorman MJ, Rossignol E, Shin S, Yuan D, Fontana L, Mukerji SS, Lauffenburger DA, Gabuzda D, and Alter G
- Subjects
- Central Nervous System, HIV Antibodies, Humans, Neurocognitive Disorders complications, HIV Infections, HIV-1
- 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 Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2022
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