The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.

TitleThe link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.
Publication TypeJournal Article
Year of Publication2023
AuthorsCheng, D, Luo, Z, Fitting, S, Stoops, W, Heath, SL, Ndhlovu, LC, Jiang, W
JournalNeuroImmune Pharm Ther
Volume2
Issue1
Pagination71-79
Date Published2023 Mar 25
ISSN2750-6665
Abstract

BACKGROUND: We recently reveal that anti-CD4 autoantibodies contribute to blunted CD4+ T cell reconstitution in HIV+ individuals on antiretroviral therapy (ART). Cocaine use is common among HIV+ individuals and is associated with accelerated disease progression. However, the mechanisms underlying cocaine-induced immune perturbations remain obscure.

METHODS: We evaluated plasma levels of anti-CD4 IgG and markers of microbial translocation, as well as B-cell gene expression profiles and activation in HIV+ chronic cocaine users and non-users on suppressive ART, as well as uninfected controls. Plasma purified anti-CD4 IgGs were assessed for antibody-dependent cytotoxicity (ADCC).

RESULTS: HIV+ cocaine users had increased plasma levels of anti-CD4 IgGs, lipopolysaccharide (LPS), and soluble CD14 (sCD14) versus non-users. An inverse correlation was observed in cocaine users, but not non-drug users. Anti-CD4 IgGs from HIV+ cocaine users mediated CD4+ T cell death through ADCC in vitro. B cells from HIV+ cocaine users exhibited activation signaling pathways and activation (cycling and TLR4 expression) related to microbial translocation versus non-users.

CONCLUSIONS: This study improves our understanding of cocaine associated B cell perturbations and immune failure and the new appreciation for autoreactive B cells as novel therapeutic targets.

DOI10.1515/nipt-2022-0019
Alternate JournalNeuroImmune Pharm Ther
PubMed ID37027536
PubMed Central IDPMC10070012