CCR2 on CD14+CD16+ monocytes is a biomarker of HIV-associated neurocognitive disorders

Dionna W. Williams, Desiree Byrd, Leah H. Rubin, Kathryn Anastos, Susan Morgello, Joan W. Berman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective: To evaluate C-Cchemokine 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.

Original languageEnglish (US)
Article numbere36
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume1
Issue number3
DOIs
StatePublished - Oct 1 2014

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Monocytes
Biomarkers
HIV
Blood-Brain Barrier
Population
Ligands
Transendothelial and Transepithelial Migration
Neurocognitive Disorders
Chemokine CCL2
CD4 Lymphocyte Count
Viral Load
Sample Size
Cognition
Cell Movement
T-Lymphocytes

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

CCR2 on CD14+CD16+ monocytes is a biomarker of HIV-associated neurocognitive disorders. / Williams, Dionna W.; Byrd, Desiree; Rubin, Leah H.; Anastos, Kathryn; Morgello, Susan; Berman, Joan W.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 1, No. 3, e36, 01.10.2014.

Research output: Contribution to journalArticle

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T1 - CCR2 on CD14+CD16+ monocytes is a biomarker of HIV-associated neurocognitive disorders

AU - Williams, Dionna W.

AU - Byrd, Desiree

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AU - Morgello, Susan

AU - Berman, Joan W.

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N2 - Objective: To evaluate C-Cchemokine 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.

AB - Objective: To evaluate C-Cchemokine 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.

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