title: A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations.
abstract: OBJECTIVE
  In spite of effective antiretroviral therapy (ART), cognition is impaired in upwards of 35% of the HIV-infected population. We investigated a possible link between peripheral immune activation and brain metabolite concentrations.
  
  
  METHODS
  Thirty-five HIV-seropositive (HIV+) and eight HIV-seronegative adults were recruited to this cross-sectional study. All HIV-positive patients were on ART or a treatment interruption. Participants were evaluated for monocyte gene expression, cognitive status, and brain metabolite concentrations using 4-Tesla short echo-time proton magnetic resonance spectroscopy. Absolute concentrations of brain metabolites in the frontal white matter (FWM), anterior cingulate cortex (ACC), and basal ganglia were derived and related to monocyte gene expression and global deficit scores.
  
  
  RESULTS
  Analysis of monocyte gene arrays revealed an interferon (IFN)-α-induced activation phenotype. Fourteen genes having the greatest fold increase in response to HIV were IFN genes. Monocyte activation as measured by gene expression profiles strongly correlated with lower N-acetylaspartate (NAA) in FWM. The IFN response gene Interferon-gamma inducible protein-10 (IP-10) was activated in monocytes from HIV individuals and strongly correlated with plasma protein levels. Plasma IP-10 correlated significantly and inversely with ACC NAA, which was lower in HIV-positive patients with mild compared to no cognitive impairment.
  
  
  CONCLUSIONS
  Chronic peripheral immune activation driven by a type 1 IFN correlates with neuronal injury in FWM and ACC and cognitive dysfunction. Easily measured IFN-induced blood markers may be clinically significant in following early neural cell damage.
authors.affiliation: Department of Laboratory Medicine, Veterans Affairs Medical Center, San Francisco, 94121, USA. lynn.pulliam@ucsf.edu
authors.forename: Lynn
authors.initials: L
authors.lastname: Pulliam
authors.forename: Hans
authors.initials: H
authors.lastname: Rempel
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Linda
authors.initials: L
authors.lastname: Abadjian
authors.forename: Cyrus
authors.initials: C
authors.lastname: Calosing
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Meyerhoff
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype
chemical_list: D007372:Interferons