Title | The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Cheng, D, Luo, Z, Fitting, S, Stoops, W, Heath, SL, Ndhlovu, LC, Jiang, W |
Journal | NeuroImmune Pharm Ther |
Volume | 2 |
Issue | 1 |
Pagination | 71-79 |
Date Published | 2023 Mar 25 |
ISSN | 2750-6665 |
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. |
DOI | 10.1515/nipt-2022-0019 |
Alternate Journal | NeuroImmune Pharm Ther |
PubMed ID | 37027536 |
PubMed Central ID | PMC10070012 |