Publication Abstract Display | Type: Published Manuscript | Title: Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. | Authors: Kamat A, Lyons JL, Misra V, Uno H, Morgello S, Singer EJ, Gabuzda D | Year: 2012 | Publication: Basic and Translational Science | Volume: 60 Issue: 3 Pages: 234-243 | Abstract:Background: Activated monocytes/macrophages play a role in
severe forms of HIV-associated neurocognitive disorders (HAND),
but little is known about the mechanisms driving milder forms that
are prevalent despite combination antiretroviral therapy (cART). To
examine relationships of monocyte activation markers to HAND of
varying severity, we compared plasma and cerebrospinal fluid (CSF)
biomarker levels with neurocognitive test scores in HIV+ subjects.
Methods: Plasma and CSF soluble CD14 (sCD14), CCL2, and
interleukin (IL) 6 were measured by enzyme-linked immunosorbent
assay in 67 HIV+ subjects with nadir CD4 ,300, and CSF inflammatory
biomarkers were measured by multiplex assay in 14 subjects
on suppressive cART.
Results: Eighty-two percent were on cART, with 31% having
undetectable plasma viral load (VL). CSF sCD14 was increased in
subjects with impaired neurocognitive testing (P = 0.02), correlated
inversely with global T scores in subjects with detectable but not
undetectable plasma VL (P = 0.02), and yielded higher area under
the receiver operating characteristic curve values for predicting
impaired T scores (0.659) than plasma or CSF VL and current or
nadir CD4 counts in single-marker and multivariate models. CSF
sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and interferon (IFN)
gamma were increased in subjects on suppressive cART regardless
of cognitive status and predicted patient class in unsupervised analyses,
with IL-8, CCL2, and IFNg explaining most of the variance.
Conclusions: CSF sCD14 is associated with impaired neurocognitive
testing in patients with HIV on nonsuppressive cART,
suggesting potential utility as a biomarker to monitor HAND
progression. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and
IFNg remain elevated in patients on suppressive cART regardless of
cognitive status, implying ongoing intrathecal inflammation even in
the absence of clinical manifestations. |
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