Cerebrospinal fluid extracellular vesicles and neurofilament light protein as biomarkers of central nervous system injury in HIV-infected patients on antiretroviral therapy.

TitleCerebrospinal fluid extracellular vesicles and neurofilament light protein as biomarkers of central nervous system injury in HIV-infected patients on antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2019
AuthorsGuha, D, Mukerji, SS, Chettimada, S, Misra, V, Lorenz, DR, Morgello, S, Gabuzda, D
JournalAIDS
Volume33
Issue4
Pagination615-625
Date Published03/2019
ISSN1473-5571
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 (< 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.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.

DOI10.1097/QAD.0000000000002121
Alternate JournalAIDS
PubMed ID30557159
PubMed Central IDPMC6399073
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U24 MH100925 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
R01 MH097659 / MH / NIMH NIH HHS / United States
T32 AG000222 / AG / NIA NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
K23 MH115812 / MH / NIMH NIH HHS / United States
R01 MH110259 / MH / NIMH NIH HHS / United States
R01 DA040391 / DA / NIDA NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States