Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection.
Title | Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Spatola, M, Loos, C, Cizmeci, D, Webb, N, Gorman, MJ, Rossignol, E, Shin, S, Yuan, D, Fontana, L, Mukerji, SS, Lauffenburger, DA, Gabuzda, D, Alter, G |
Journal | J Infect Dis |
Volume | 226 |
Issue | 4 |
Pagination | 738-750 |
Date Published | 2022 Sep 04 |
ISSN | 1537-6613 |
Keywords | CHARTER, External |
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. |
DOI | 10.1093/infdis/jiac138 |
Alternate Journal | J Infect Dis |
PubMed ID | 35417540 |
PubMed Central ID | PMC9441210 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States K23 MH115812 / MH / NIMH NIH HHS / United States 3R37AI080289-11S1 / NH / NIH HHS / United States R56 MH115853 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States U24MH100931 / NS / NINDS NIH HHS / United States |