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

Overview

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.

publication date

  • November 26, 2018

Research

keywords

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Central Nervous System
  • Galectins
  • HIV Infections
  • RNA, Viral
  • Receptors, Cell Surface
  • Viremia

Identity

PubMed Central ID

  • PMC6506351

Scopus Document Identifier

  • 85057553391

Digital Object Identifier (DOI)

  • 10.1093/infdis/jix013

PubMed ID

  • 30478799

Additional Document Info

volume

  • 25

issue

  • 2