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Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.

Journal article
Authors Birgitta Anesten
Aylin Yilmaz
Henrik Zetterberg
Lars Hagberg
Staffan Nilsson
Bruce J Brew
Dietmar Fuchs
Richard W Price
Magnus Gisslén
Published in Neurology, Neuroimmunology & Neuroinflammation
Volume 3
Issue 6
Pages e300
ISSN 2332-7812
Publication year 2016
Published at Department of Mathematical Sciences, Applied Mathematics and Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Infectious Medicine
Pages e300
Language en
Links dx.doi.org/10.1212/NXI.000000000000...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurochemistry

Abstract

Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.

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