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

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.