Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection.
ART
Fc receptors
HIV-associated neurocognitive disorders
NK activation
antibody functions
cerebrospinal fluid
complement deposition
phagocytosis
plasma
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
04 09 2022
04 09 2022
Historique:
received:
13
09
2021
accepted:
07
04
2022
pubmed:
14
4
2022
medline:
9
9
2022
entrez:
13
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35417540
pii: 6568136
doi: 10.1093/infdis/jiac138
pmc: PMC9441210
doi:
Substances chimiques
HIV Antibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
738-750Subventions
Organisme : NIMH NIH HHS
ID : U24 MH100929
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100925
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH115812
Pays : United States
Organisme : NIH HHS
ID : 3R37AI080289-11S1
Pays : United States
Organisme : NIMH NIH HHS
ID : R56 MH115853
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100930
Pays : United States
Organisme : NIMH NIH HHS
ID : HHSN271201000030C
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100931
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100928
Pays : United States
Organisme : NIMH NIH HHS
ID : HHSN271201000036C
Pays : United States
Organisme : NINDS NIH HHS
ID : U24MH100931
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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