Abstract

Despite the use of antiretroviral drugs HIV associated neurocognitive disorders (HAND) are still common in HIV-seropositive patients. Identification of HIV patients with cognitive impairment in early-stage might benefit a great deal from disease progression monitoring and treatment adjustment. Intercellular adhesion molecule-5 (ICAM5), characteristically expressed on neuron, may suppress immune functions by inhibition of T cell activation in central nervous system. Previous studies have shown that ICAM5 could be detected in patients with brain injury. To investigate the relationship between cognitive impairment and ICAM5 in HIV patients, we compared soluble ICAM5 levels in paired CSF and plasma specimens from HIV-infected individuals with or without neurocognitive impairment. sICAM5 concentrations were measured by ICAM5 ELISA kit. A total of 41 Patients were classified into HIV infected with normal cognition (HIV-NC) and impaired cognition groups (HIV-CI) based on Memorial Sloan-Kettering Scale. CSF and plasma levels of sICAM5 in HIV-CI patients were significantly higher than HIV-NC group (p<0.0001, p=0.0054 respectively). sICAM5 concentrations in plasma strongly correlated with sICAM5 in CSF (r=0.7250, p<0.0001) and S100B in CSF (r=0.3812, p<0.0139). Among 6 follow-up patients we found that sICAM5 levels in CSF and plasma might change consistently with HAND progression. In summary, we have shown that the expressions of sICAM5 in CSF and plasma may correlate with neurocognitive impairment in HIV infected patients. The elevation of sICAM5 in plasma were correspond with that in CSF as a consequence of blood-brain barrier permeability changes. ICAM5 can serve as a potential and readily accessible biomarker to predict HIV associated neurocognitive disorder.

Highlights

  • Human immunodeficiency virus (HIV) enters the central nervous system (CNS) early after infection and gives rise to HIV-associated neurocognitive disorder (HAND), which are characterized by a wild spectrum of behavioral, cognitive, and motor dysfunctions

  • There was no significant difference in Cerebrospinal fluid (CSF) or plasma HIV-1 RNA concentration between these groups, as well as in blood CD4+ T cell counts

  • intercellular adhesion molecule-5 (ICAM5) can be cleaved under several pathological conditions in the brain and its soluble form soluble ICAM-5 (sICAM5), known as telencephalin, is strictly CNS tissue origin. sICAM5 has been detected in experimental hypoxic-ischemic brain injury, traumatic brain injury, temporal lobe epilepsy, Alzheimer’s disease and herpes simplex encephalitis [26,27,28,29,30,31,32,33]

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Summary

Introduction

Human immunodeficiency virus (HIV) enters the central nervous system (CNS) early after infection and gives rise to HIV-associated neurocognitive disorder (HAND), which are characterized by a wild spectrum of behavioral, cognitive, and motor dysfunctions. ICAM-5 is characteristically expressed on the soma and dendrites of neuron. Through the ICAM5-CD11a/CD18 (LFA-1) interaction, Neurons diminish TCR dependent T-cell activation in CNS. We verified that ICAM5 expressed on soma and neurite of neurons cultured in vitro, and neurons treated with matrix metalloproteinases (MMPs) became more vulnerable to HIV-1 gp120. These findings suggest that ICAM-5 may have the potential protective effect against HIV induced neuro-inflammation or neurodegeneration. These findings suggest that ICAM-5 may have the potential protective effect against HIV induced neuro-inflammation or neurodegeneration. sICAM5 might reflect the damage of vulnerable telencephalic neurons in HAND

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