Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection. (13th April 2022)

• Record Type: Journal Article
• Authors: Spatola, Marianna; Loos, Carolin; Cizmeci, Deniz; Webb, Nicholas; Gorman, Matthew J; Rossignol, Evan; Shin, Sally; Yuan, Dansu; Fontana, Laura; Mukerji, Shibani S; Lauffenburger, Douglas A; Gabuzda, Dana; Alter, Galit
• Is Part Of: Journal of infectious diseases. Volume 226:Number 4(2022)
• Page Start: 738
• Page End: 750
• Publication Date: 2022-04-13
• Subjects: cerebrospinal fluid -- plasma -- antibody functions -- complement deposition -- phagocytosis -- NK activation -- Fc receptors -- ART -- HIV-associated neurocognitive disorders; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac138
• Languages: English
• ISSNs: 0022-1899

Abstract

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 : The role of HIV-specific antibodies in the brain during chronic infection is unclear. Here we found striking compartmentalization of HIV-specific antibodies, marked by a unique and highly selective enrichment of poorly functional IgG1 and IgG3 antibodies in the CSF.