title: Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis : CSF Biomarkers of SIV Encephalitis.
abstract: Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA, 15261, USA. stephaniebissel@pitt.edu.
authors.forename: Stephanie J
authors.identifier: 0000-0002-7376-2327
authors.initials: SJ
authors.lastname: Bissel
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.affiliation: Department of Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Nyaundi
authors.affiliation: Department of Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Murphey-Corb
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, PA, 15261, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid* / Q000473:pathology; D008254:Macaca nemestrina; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D019562:Viral Load / Q000502:physiology*
chemical_list: D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1
keywords: Biomarker; Cerebrospinal fluid; Encephalitis; Human immunodeficiency virus; Simian immunodeficiency virus; YKL40