Date Published:
2022 Sep 04

Publication Type:
Journal Article

Authors:

M. Spatola
C. Loos
D. Cizmeci
N. Webb
M.J. Gorman
E. Rossignol
S. Shin
D. Yuan
L. Fontana
S.S. Mukerji
D.A. Lauffenburger
D. Gabuzda
G. Alter

Secondary:
J Infect Dis

Volume:
226

Pagination:
738-750

Issue:
4

PMID:
35417540

URL:
https://pubmed.ncbi.nlm.nih.gov/35417540

DOI:
10.1093/infdis/jiac138

Keywords:
CHARTER;External

Abstract:
<p>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.</p>