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

TitleCCR2 on CD14(+)CD16(+) monocytes is a biomarker of HIV-associated neurocognitive disorders.
Publication TypeJournal Article
Year of Publication2014
AuthorsWilliams, DW, Byrd, D, Rubin, LH, Anastos, K, Morgello, S, Berman, JW
JournalNeurol Neuroimmunol Neuroinflamm
Volume1
Issue3
Paginatione36
Date Published2014 Oct
ISSN2332-7812
KeywordsExternal
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.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/25340088
DOI10.1212/NXI.0000000000000036
Alternate JournalNeurol Neuroimmunol Neuroinflamm
PubMed ID25340088
PubMed Central IDPMC4204222
Grant ListR25 MH080663 / MH / NIMH NIH HHS / United States
T32 AI070117 / AI / NIAID NIH HHS / United States
U01 AI035004 / AI / NIAID NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States