CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA

reseeding of CNS reservoirs?

Mike Veenstra, Desiree A. Byrd, Matilde Inglese, Korhan Buyukturkoglu, Dionna W. Williams, Lazar Fleysher, Ming Li, Lucio Gama, Rosiris León-Rivera, Tina M. Calderon, Janice E. Clements, Susan Morgello, Joan W. Berman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 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 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. 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 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.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJournal of NeuroImmune Pharmacology
DOIs
StateAccepted/In press - Jul 6 2018

Fingerprint

Monocytes
HIV
DNA
Creatine
Neurocognitive Disorders
Blood Cells
Biomarkers
Caudate Nucleus
Chemokine Receptors
Glutamine
Glutamic Acid
Macrophages

Keywords

  • CCR2
  • CD14CD16 Monocytes
  • ddPCR
  • HAND
  • HIV
  • MRI/MRS

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA : reseeding of CNS reservoirs? / Veenstra, Mike; Byrd, Desiree A.; Inglese, Matilde; Buyukturkoglu, Korhan; Williams, Dionna W.; Fleysher, Lazar; Li, Ming; Gama, Lucio; León-Rivera, Rosiris; Calderon, Tina M.; Clements, Janice E.; Morgello, Susan; Berman, Joan W.

In: Journal of NeuroImmune Pharmacology, 06.07.2018, p. 1-14.

Research output: Contribution to journalArticle

Veenstra, Mike ; Byrd, Desiree A. ; Inglese, Matilde ; Buyukturkoglu, Korhan ; Williams, Dionna W. ; Fleysher, Lazar ; Li, Ming ; Gama, Lucio ; León-Rivera, Rosiris ; Calderon, Tina M. ; Clements, Janice E. ; Morgello, Susan ; Berman, Joan W. / CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA : reseeding of CNS reservoirs?. In: Journal of NeuroImmune Pharmacology. 2018 ; pp. 1-14.
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abstract = "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 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 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. 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 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.",
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AU - Byrd, Desiree A.

AU - Inglese, Matilde

AU - Buyukturkoglu, Korhan

AU - Williams, Dionna W.

AU - Fleysher, Lazar

AU - Li, Ming

AU - Gama, Lucio

AU - León-Rivera, Rosiris

AU - Calderon, Tina M.

AU - Clements, Janice E.

AU - Morgello, Susan

AU - Berman, Joan W.

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