Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals.

TitleElevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals.
Publication TypeJournal Article
Year of Publication2018
AuthorsPremeaux, TA, D'Antoni, ML, Abdel-Mohsen, M, Pillai, SK, Kallianpur, KJ, Nakamoto, BK, Agsalda-Garcia, M, Shiramizu, B, Shikuma, CM, Gisslén, M, Price, RW, Valcour, V, Ndhlovu, LC
JournalJ Neurovirol
Date Published11/2018
ISSN1538-2443
KeywordsExternal
Abstract

We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older > 40 years and younger < 40 years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p < 0.05). CSF Gal-9 positively correlated with age in all groups (p < 0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (β = 0.33; p < 0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p < 0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p < 0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p < 0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.

DOI10.1007/s13365-018-0696-3
Alternate JournalJ. Neurovirol.
PubMed ID30478799
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U24 MH100925 / MH / NIMH NIH HHS / United States
U54 NS043049 / NS / NINDS NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
MH098759 / / Foundation for the National Institutes of Health /
1R01MH112457-01 / / Foundation for the National Institutes of Health /
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH112457 / MH / NIMH NIH HHS / United States
U54 MD007584 / MD / NIMHD NIH HHS / United States
ALFGBG-717531 / / Swedish State support for Clinical Research /
P01 DA026134 / / Foundation for the National Institutes of Health /
U54NS43049 / / Foundation for the National Institutes of Health /
K24 MH098759 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
R01 NS094067 / / Foundation for the National Institutes of Health /
P01 DA026134 / DA / NIDA NIH HHS / United States
R01 NS094067 / NS / NINDS NIH HHS / United States