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Cerebrospinal fluid levels of glial marker YKL-40 strongly associated with axonal injury in HIV infection

Journal article
Authors Linn Hermansson
Aylin Yilmaz
M Axelsson
Kaj Blennow
D. Fuchs
Lars Hagberg
Jan Lycke
Henrik Zetterberg
Magnus Gisslén
Published in Journal of Neuroinflammation
Volume 16
Issue 1
ISSN 1742-2094
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Institute of Biomedicine, Department of Infectious Medicine
Language en
Links dx.doi.org/10.1186/s12974-019-1404-...
Keywords HIV, Cerebrospinal fluid, YKL-40, Neurofilament protein, simian immunodeficiency virus, neuronal injury, microglial activation, protein, astrocytes, neopterin, brain, neuropathogenesis, expression, biomarker, Immunology, Neurosciences & Neurology
Subject categories Immunology, Neuroscience

Abstract

BackgroundHIV-1 infects the central nervous system (CNS) shortly after transmission. This leads to a chronic intrathecal immune activation. YKL-40, a biomarker that mainly reflects activation of astroglial cells, has not been thoroughly investigated in relation to HIV. The objective of our study was to characterize cerebrospinal fluid (CSF) YKL-40 in chronic HIV infection, with and without antiretroviral treatment (ART).MethodsYKL-40, neopterin, and the axonal marker neurofilament light protein (NFL) were analyzed with ELISA in archived CSF samples from 120 HIV-infected individuals (85 untreated neuroasymptomatic patients, 7 with HIV-associated dementia, and 28 on effective ART) and 39 HIV-negative controls.ResultsCSF YKL-40 was significantly higher in patients with HIV-associated dementia compared to all other groups. It was also higher in untreated neuroasymptomatic individuals with CD4 cell count <350 compared to controls. Significant correlations were found between CSF YKL-40 and age (r=0.38, p<0.001), CD4 (r=-0.36, p<0.001), plasma HIV RNA (r=0.35, p<0.001), CSF HIV RNA (r=0.35, p<0.001), CSF neopterin (r=0.40, p<0.001), albumin ratio (r=0.44, p<0.001), and CSF NFL (r=0.71, p<0.001). Age, CD4 cell count, albumin ratio, and CSF HIV RNA were found as independent predictors of CSF YKL-40 concentrations in multivariable analysis. In addition, CSF YKL-40 was revealed as a strong independent predictor of CSF NFL together with age, CSF neopterin, and CD4 cell count.ConclusionsCSF YKL-40 is a promising biomarker candidate for understanding the pathogenesis of HIV in the CNS. The strong correlation between CSF YKL-40 and NFL suggests a pathogenic association between astroglial activation and axonal injury, and implies its utility in assessing the prognostic value of YKL-40.

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