title: Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection.
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 IFNγ 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 IFNγ remain elevated in patients on suppressive cART regardless of cognitive status, implying ongoing intrathecal inflammation even in the absence of clinical manifestations.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anupa
authors.initials: A
authors.lastname: Kamat
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Lyons
authors.forename: Vikas
authors.initials: V
authors.lastname: Misra
authors.forename: Hajime
authors.initials: H
authors.lastname: Uno
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000523:psychology / Q000821:virology; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000097:blood / Q000134:cerebrospinal fluid; D003071:Cognition; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012367:RNA, Viral