2016
DOI: 10.1007/s13365-016-0466-z
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Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals

Abstract: HIV-associated neurocognitive disorders (HAND) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive p… Show more

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Cited by 25 publications
(22 citation statements)
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“…A recent retrospective neuropathology study of simian immunodeficiency virus (SIV)-infected pigtailed macaques on ART demonstrated significant prevalence of lymphocyte-dominant inflammation in the CNS [ 62 ], suggesting that adaptive immune responses may persist in the CNS in HIV-infected ART-treated individuals and may contribute to neuronal dysfunction and subsequent neurocognitive decline. Moreover, human studies have demonstrated that increased T-lymphocyte activation [ 63 , 64 ] and type I interferon responses [ 24 , 65 , 66 ] associate with more pronounced neurocognitive dysfunction in HIV-infected individuals.…”
Section: Discussionmentioning
confidence: 99%
“…A recent retrospective neuropathology study of simian immunodeficiency virus (SIV)-infected pigtailed macaques on ART demonstrated significant prevalence of lymphocyte-dominant inflammation in the CNS [ 62 ], suggesting that adaptive immune responses may persist in the CNS in HIV-infected ART-treated individuals and may contribute to neuronal dysfunction and subsequent neurocognitive decline. Moreover, human studies have demonstrated that increased T-lymphocyte activation [ 63 , 64 ] and type I interferon responses [ 24 , 65 , 66 ] associate with more pronounced neurocognitive dysfunction in HIV-infected individuals.…”
Section: Discussionmentioning
confidence: 99%
“…HIV-infected adult subjects without subacute cognitive decline over the prior 30 days AND were off cART (due to compliance, side effects, or insurance related issues) were recruited at the Emory University Center for AIDS Research (CFAR) as previously described 60 . Briefly, each subject underwent standard medical evaluation and blood tests (TSH, vitamin B12, serum cryptococcal antigen) to rule out reversible causes of cognitive impairment, followed by standardized neuropsychological testing according to the most recent HAND criteria 12 .…”
Section: Methodsmentioning
confidence: 99%
“…In all subjects, plasma and CSF samples were obtained on the same day as neuropsychological analysis 60 . Plasma samples were centrifuged, aliquoted, labeled, and stored at −80 °C until analysis.…”
Section: Methodsmentioning
confidence: 99%
“…Interferon alpha (IFNα) has been implicated in contributing to the neuropathology observed in HAND patients as high CSF concentrations of this cytokine have been reported to be positively correlated with cognitive impairment in HIV+ individuals [ 187 , 273 275 ]. It is thought that IFNα leads to dendritic simplification through a mechanism mediated by INFAR and NMDA receptors, with the 2A subunit of the NMDA receptor playing a vital role in IFNα-mediated neurotoxicity [ 276 ].…”
Section: Potential Pharmacological Therapies For Handmentioning
confidence: 99%