UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation

Cheng, D; Luo, Z; Fu, X; Stephenson, S; Di Germanio, C; Norris, PJ; Fuchs, D; ... Jiang, W; + view all (2022) Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation. Microbiology Spectrum , 10 (1) , Article e0197521. 10.1128/spectrum.01975-21. Green open access

[thumbnail of Zetterberg_Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation_VoR.pdf]
Preview
Text
Zetterberg_Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation_VoR.pdf - Published Version

Download (1MB) | Preview

Abstract

The mechanisms of persistent central nervous system (CNS) inflammation in people with HIV (PWH) despite effective antiretroviral therapy (ART) are not fully understood. We have recently shown that plasma anti-CD4 IgGs contribute to poor CD4+ T cell recovery during suppressive ART via antibody-mediated cytotoxicity (ADCC) against CD4+ T cells, and that plasma anti-CD4 IgG levels are associated with worse cognitive performance and specific brain area atrophy. However, the role of anti-CD4 IgGs in neuroinflammation remains unclear. In the current study, plasma and cerebrospinal fluid (CSF) samples from 31 ART-naive and 26 treated, virologically suppressed PWH, along with 16 HIV-seronegative controls, were evaluated for CSF levels of anti-CD4 IgG, white blood cell (WBC) counts, soluble biomarkers of neuroinflammation, and neurofilament light chain (NfL). We found that 37% of the PWH exhibited elevated CSF anti-CD4 IgG levels, but few or none of the PWH were observed with elevated CSF anti-CD4 IgM, anti-CD8 IgG, or anti-double-strand DNA IgG. CSF anti-CD4 IgG levels in PWH were directly correlated with neuroinflammation (WBC counts, neopterin, and markers of myeloid cell activation), but not with CSF NfL levels. Using cells from one immune nonresponder to ART, we generated a pathogenic anti-CD4 monoclonal IgG (JF19) presenting with ADCC activity; JF19 induced the production of soluble CD14 (sCD14) and interleukin-8 (IL-8) in human primary monocyte-derived macrophages via CD4 binding in vitro. This study demonstrates for the first time that elevated CSF anti-CD4 IgG levels present in a subgroup of PWH which may play a role in neuroinflammation in HIV. IMPORTANCE This study reports that an autoantibody presents in the CNS of HIV patients and that its levels in the CSF correlate with some markers of neuroinflammation.

Type: Article
Title: Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/spectrum.01975-21
Publisher version: https://doi.org/10.1128/spectrum.01975-21
Language: English
Additional information: © 2022 Cheng et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Keywords: HIV, HIV-1 infection, anti-CD4 IgG, anti-CD4 autoantibody, cerebrospinal fluid, neuroinflammation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10141701
Downloads since deposit
32Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item