title: CCR2 on CD14(+)CD16(+) monocytes is a biomarker of HIV-associated neurocognitive disorders.
abstract: OBJECTIVE
  To evaluate C-C chemokine receptor type 2 (CCR2) on monocyte subsets as a prognostic peripheral blood biomarker of HIV-associated neurocognitive disorders (HAND).
  
  
  METHODS
  We characterized monocyte populations in HIV-infected individuals with and without HAND from 2 cohorts and assessed their transmigration across an in vitro model of the human blood-brain barrier (BBB). We examined CCR2 expression among the monocyte populations as a prognostic/predictive biomarker of HAND and its functional consequences in facilitating monocyte diapedesis.
  
  
  RESULTS
  We determined that CCR2 was significantly increased on CD14(+)CD16(+) monocytes in individuals with HAND compared to infected people with normal cognition. CCR2 remained elevated irrespective of the severity of cognitive impairment, combined antiretroviral therapy status, viral load, and current or nadir CD4 T-cell count. There was no association between CCR2 on other monocyte populations and HAND. There was a functional consequence to the increase in CCR2, as CD14(+)CD16(+) monocytes from individuals with HAND transmigrated across our model of the human BBB in significantly higher numbers in response to its ligand chemokine (C-C) motif ligand 2 (CCL2) compared to the cell migration that occurred in people with no cognitive deficits. It should be noted that our study had the limitation of a smaller sample size of unimpaired individuals. In contrast, there was no difference in the transmigration of other monocyte subsets across the BBB in response to CCL2 in seropositive individuals with or without HAND.
  
  
  CONCLUSIONS
  Our findings indicate CCR2 on CD14(+)CD16(+) monocytes is a novel peripheral blood biomarker of HAND.
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Dionna W
authors.initials: DW
authors.lastname: Williams
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Desiree
authors.initials: D
authors.lastname: Byrd
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Leah H
authors.initials: LH
authors.lastname: Rubin
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Departments of Pathology (D.W.W., J.W.B.), Medicine and Epidemiology & Population Health (K.A.), and Microbiology and Immunology (J.W.B.), The Albert Einstein College of Medicine, Bronx, NY; Departments of Neurology (D.B., S.M.), Neuroscience (S.M.), and Pathology (S.M.), The Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Psychiatry (L.H.R.), University of Illinois at Chicago, IL.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman