Cerebrospinal fluid extracellular vesicles and neurofilament light protein as biomarkers of central nervous system injury in HIV-infected patients on antiretroviral therapy.
AIDS Dementia Complex
/ pathology
Anti-Retroviral Agents
/ therapeutic use
Antiretroviral Therapy, Highly Active
Biomarkers
/ cerebrospinal fluid
Central Nervous System
Cerebrospinal Fluid
/ chemistry
Cross-Sectional Studies
Extracellular Vesicles
Female
HIV Infections
/ complications
Humans
Longitudinal Studies
Male
Middle Aged
Neurofilament Proteins
/ analysis
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
pubmed:
18
12
2018
medline:
15
4
2020
entrez:
18
12
2018
Statut:
ppublish
Résumé
The relationship of cerebrospinal fluid (CSF) extracellular vesicles to neurocognitive impairment (NCI) in HIV-infected individuals is unclear. Here, we characterize CSF extracellular vesicles and their association with central nervous system (CNS) injury related biomarkers [neurofilament light (NFL), S100B, neopterin] and NCI in HIV-positive individuals on combination antiretroviral therapy (cART). A cross-sectional and longitudinal study of CSF samples from HIV-positive individuals on cART. NFL, S100B and neopterin were measured by ELISA in 190 CSF samples from 112 individuals (67 HIV-positive and 45 HIV-negative). CSF extracellular vesicles were isolated and characterized by electron microscopy, nanoparticle tracking analysis, immunoblotting for exosome markers (CD9, CD63, CD81, FLOT-1) and ELISA for HLA-DR. HIV-positive individuals had median age 52 years, 67% with suppressed plasma viral load (< 50 copies/ml), median CD4 nadir 66 cells/μl and CD4 cell count 313 cells/μl. CSF NFL, S100B and neopterin levels were higher in HIV-positive vs. HIV-negative individuals, and nonsuppressed vs. suppressed HIV-positive individuals. Although CSF NFL and S100B levels were higher in NCI vs. unimpaired HIV-positive individuals (P < 0.05), only NFL was associated with NCI in adjusted models (P < 0.05). CSF extracellular vesicles were increased in HIV-positive vs. HIV-negative individuals, and NCI vs. unimpaired HIV-positive individuals (P < 0.05), and correlated positively with NFL (P < 0.001). HLA-DR was enriched in CSF extracellular vesicles from HIV-positive individuals with NCI (P < 0.05), suggesting that myeloid cells are a potential source of CSF extracellular vesicles during HIV infection. Increased CSF extracellular vesicles correlate with neuronal injury biomarker NFL in cART-treated HIV-positive individuals with neurocognitive impairment, suggesting potential applications as novel biomarkers of CNS injury.
Identifiants
pubmed: 30557159
doi: 10.1097/QAD.0000000000002121
pmc: PMC6399073
mid: NIHMS1003681
doi:
Substances chimiques
Anti-Retroviral Agents
0
Biomarkers
0
Neurofilament Proteins
0
neurofilament protein L
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
615-625Subventions
Organisme : NIMH NIH HHS
ID : U24 MH100929
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100925
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100931
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097659
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG000222
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100928
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH115812
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110259
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040391
Pays : United States
Organisme : NIMH NIH HHS
ID : U24 MH100930
Pays : United States
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