Cerebrospinal fluid extracellular vesicles and neurofilament light protein as biomarkers of central nervous system injury in HIV-infected patients on antiretroviral therapy.
AIDS
; 33(4): 615-625, 2019 03 15.
Article
em En
| MEDLINE
| ID: mdl-30557159
ABSTRACT
OBJECTIVE:
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).DESIGN:
A cross-sectional and longitudinal study of CSF samples from HIV-positive individuals on cART.METHODS:
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.RESULTS:
HIV-positive individuals had median age 52 years, 67% with suppressed plasma viral load (< 50âcopies/ml), median CD4 nadir 66âcells/µl and CD4 cell count 313âcells/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 (Pâ<â0.05), only NFL was associated with NCI in adjusted models (Pâ<â0.05). CSF extracellular vesicles were increased in HIV-positive vs. HIV-negative individuals, and NCI vs. unimpaired HIV-positive individuals (Pâ<â0.05), and correlated positively with NFL (Pâ<â0.001). HLA-DR was enriched in CSF extracellular vesicles from HIV-positive individuals with NCI (Pâ<â0.05), suggesting that myeloid cells are a potential source of CSF extracellular vesicles during HIV infection.CONCLUSION:
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Infecções por HIV
/
Líquido Cefalorraquidiano
/
Complexo AIDS Demência
/
Proteínas de Neurofilamentos
/
Vesículas Extracelulares
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article