title: Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients.
abstract: The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS inflammation following the first clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 ± 8.2 years (mean ± SD)] enrolled in a multi-center study of interferon β1-a treatment following the first demyelinating event. Blood and cerebrospinal fluid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profile and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P ≤ 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ (P < 0.001) and with CSF CD80+CD19+ (P = 0.007) cell frequencies. Higher serum HDL is associated with lower levels of BBB injury and decreased CD80+ and CD80+CD19+ cell extravasation into the CSF. HDL may potentially inhibit the initiation and/or maintenance of pathogenic BBB injury following the first demyelinating event.
authors.affiliation: Departments of Pharmaceutical Sciences, State University of New York, Buffalo, NY.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fellows
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Uher
authors.affiliation: Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
authors.affiliation: Neurology, State University of New York, Buffalo, NY.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Institute of Immunology and Microbiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Posova
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Neurology, State University of New York, Buffalo, NY Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Departments of Pharmaceutical Sciences, State University of New York, Buffalo, NY Neurology, State University of New York, Buffalo, NY.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008076:Cholesterol, HDL / Q000097:blood*; D003711:Demyelinating Diseases; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000134:cerebrospinal fluid; D016899:Interferon-beta / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology*; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D008076:Cholesterol, HDL; D016899:Interferon-beta
keywords: apolipoproteins; cholesterol; clinically isolated syndrome; high density lipoprotein