TY - JOUR
T1 - CCR2 on Peripheral Blood CD14 + CD16 + Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA
T2 - reseeding of CNS reservoirs?
AU - Veenstra, Mike
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.
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - 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 ( 1 H-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) (r 2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r 2 = 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.
AB - 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 ( 1 H-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) (r 2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r 2 = 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.
KW - CCR2
KW - CD14 CD16 Monocytes
KW - HAND
KW - HIV
KW - MRI/MRS
KW - ddPCR
UR - http://www.scopus.com/inward/record.url?scp=85049574820&partnerID=8YFLogxK
U2 - 10.1007/s11481-018-9792-7
DO - 10.1007/s11481-018-9792-7
M3 - Article
C2 - 29981000
AN - SCOPUS:85049574820
SN - 1557-1890
VL - 14
SP - 120
EP - 133
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
IS - 1
ER -