Date Published:
07/2018
Publication Type:
Journal Article
Authors:
Secondary:
Journal of Neuroimmune Pharmacology
Volume:
14
URL:
https://pubmed.ncbi.nlm.nih.gov/
Keywords:
CCR2;CD14+CD16+ Monocytes;ddPCR;HAND;HIV;MRI/MRS
Abstract:
<p>HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14+CD16+ monocytes, particularly those that are HIV infected and express increased<br />surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14+CD16+ monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45<br />HIV infected people. We correlated CCR2 on CD14+CD16+ monocytes with cognitive status, proton magnetic resonance spectroscopy (1H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies.<br />We determined that CCR2 was increased specifically on CD14+CD16+ monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with<br />neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14+CD16+ monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14+CD16+ monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14+CD16+ monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14+CD16+ monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.<br /> </p>