학술논문

Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection.
Document Type
Journal Article
Source
Journal of Infectious Diseases. 8/15/2022, Vol. 226 Issue 4, p738-750. 13p.
Subject
*HIV infections
*RESEARCH funding
*VIRAL antibodies
*HIV
*CENTRAL nervous system
Language
ISSN
0022-1899
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. [ABSTRACT FROM AUTHOR]