Biomarkers of neurological status in HIV infection: A 3‐year study

Abstract

In this investigation, circulating cytokines and chemokines were screened as correlates of brain injury in individuals with advanced Human Immunodeficiency Virus (HIV) infection. Markers were quantified using high throughput multiplexed analysis at baseline and three years later in the clinical course. Neurological status was ascertained based on objective measurements of the brain derived in vivo with Magnetic Resonance (MR) segmentation algorithms and with Diffusion Tensor Imaging (DTI). Of the markers examined, Monocyte Chemoattractant Protein-1 (n.b. MCP-1 or CCL-2) was the most prominent correlate of brain injury. At the initial assessment, elevated MCP-1 levels correlated with alterations in brain white matter. The relationship to brain injury was more extensive three years later; MCP-1 was significantly correlated with both microstructural measures (fractional anisotropy and mean diffusivity) and with brain atrophy (in gray matter and overall parenchyma). Conclusion These findings provide further evidence of the potential importance of MCP-1 as a marker of neurological injury in HIV infection. These observations build on our prior descriptions suggesting that elevated levels of MCP-1 may be a useful predictive marker for HIV-associated neurocognitive disorder (HAND). As a potent chemoattractant, MCP-1 may mediate injury through participation in self-reinforcing cycles of chronic immune activation and cytokine/chemokine-mediated neurotoxicity.

Peripheral Neuropathy in Primary HIV Infection Associates With Systemic and Central Nervous System Immune Activation

“…CSF markers have been previously implicated in advanced stages of HIV neurological disease progression: CSF neopterin rises along with CNS HIV disease severity and decreases following ART 31 ; levels of IP-10 positively correlate with the presence of HIV-associated dementia (HAD) 32 ; and elevated MCP-1 is detected in the brain and CSF of subjects with HIV-encephalitis and HAD 33,34 . Our results support the premise that immune activation is crucial to peripheral neurological dysfunction in HIV.…”

Antiretroviral Therapy and HIV-Associated Neurocognitive Disorders

“…Several CSF markers have been utilized in an attempt to predict, diagnose and monitor the progression of HAND. Among those, as markers of immune activation, TNF-, and CCL2 levels were shown to correlate with neurological deficits in the pre-cART era Sevigny, Albert et al 2004;Ragin, Wu et al 2010); however, a more recent study did not show such a correlation for either of these markers among a cohort of patients on cART (McArthur, McDermott et al 2004). Additionally, contrary to expectations, in patients on cART regimens with high predicted CSF concentrations, the markers of inflammation and oxidative stress appear to persist (Roc, Ances et al 2007).…”

Reducing CSF Partial Volume Effects to Enhance Diffusion Tensor Imaging Metrics of Brain Microstructure

“…CSF-suppressed DTI, particularly using a NBZ approach, may help identify key mechanisms of neurological dysfunction in these clinical conditions. Similarly, while standard DTI has been utilized to examine multiple sclerosis and HIV-associated brain dysfunction, the neuroimaging signatures associated with these conditions are significantly complicated by acute inflammatory fluctuations (16,71,74), resulting in variable outcomes across studies. Application of CSF-suppressed DTI has the potential to more accurately characterize tissue microstructure in these conditions to improve clinical assessment and patient care strategies.…”