CSF extracellular vesicles and neurofilament light protein as biomarkers of CNS injury in HIV-infected patients on antiretroviral therapy

Date Published:

2018 Dec 14


OBJECTIVE: The relationship of cerebrospinal fluid (CSF) extracellular vesicles (EVs) to neurocognitive impairment (NCI) in HIV-infected individuals is unclear. Here, we characterize CSF EVs and their association with CNS injury-related biomarkers (neurofilament light [NFL], S100B, neopterin) and NCI in HIV+ subjects on combination antiretroviral therapy (cART). DESIGN: Cross-sectional and longitudinal study of CSF samples from HIV+ subjects on cART. METHODS: NFL, S100B, and neopterin were measured by ELISA in 190 CSF samples from 112 subjects (67 HIV+ and 45 HIV-). CSF EVs were isolated and characterized by electron microscopy, nanoparticle tracking analysis, immunoblotting for exosome markers (CD9, CD63, CD81, FLOT-1), and ELISA for HLA-DR. RESULTS: HIV+ subjects had median age 52 years, 67% with suppressed plasma viral load (< 50 copies/ml), median CD4 nadir 66 cells/μl and CD4 count 313 cells/μl. CSF NFL, S100B, and neopterin levels were higher in HIV+ vs. HIV- subjects, and nonsuppressed vs. suppressed HIV+ subjects. While CSF NFL and S100B levels were higher in NCI vs. unimpaired HIV+ subjects (p < 0.05), only NFL was associated with NCI in adjusted models (p < 0.05). CSF EVs were increased in HIV+ vs. HIV- subjects, and NCI vs. unimpaired HIV+ subjects (p < 0.001), and correlated positively with NFL (p < 0.001). HLA-DR was enriched in CSF EVs from HIV+ subjects with NCI (p < 0.05), suggesting myeloid cells are a potential source of CSF EVs during HIV infection. CONCLUSIONS: Increased CSF EVs correlate with neuronal injury biomarker NFL in cART-treated HIV+ individuals with neurocognitive impairment, suggesting potential applications as novel biomarkers of CNS injury.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Last updated on 12/09/2019