Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection

Author:

Spatola Marianna1,Loos Carolin12,Cizmeci Deniz12,Webb Nicholas1,Gorman Matthew J1,Rossignol Evan1,Shin Sally1,Yuan Dansu1,Fontana Laura1,Mukerji Shibani S3,Lauffenburger Douglas A2,Gabuzda Dana4ORCID,Alter Galit1

Affiliation:

1. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard , Cambridge, Massachusetts , USA

2. Massachusetts Institute of Technology , Cambridge, Massachusetts , USA

3. Massachusetts General Hospital , Boston, Massachusetts , USA

4. Dana Farber Cancer Institute , Boston, Massachusetts , USA

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.

Funder

American Academy of Neurology

Swiss National Science Foundation

Nancy Zimmerman

Mark and Lisa Schwartz

Terry and Susan Ragon

SAMANA Kay

Ragon Institute of MGH, MIT and Harvard, Massachusetts Consortium on Pathogen Readiness

National Institutes of Health

Gates Foundation

Musk Foundation

Massachusetts General Hospital

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

NIMH/NINDS

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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