Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients

J Lipid Res. 2015 Oct;56(10):2010-8. doi: 10.1194/jlr.M060970. Epub 2015 Aug 4.

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.

Keywords: apolipoproteins; cholesterol; clinically isolated syndrome; high density lipoprotein.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins / blood
  • Apolipoproteins / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology*
  • Cholesterol, HDL / blood*
  • Demyelinating Diseases
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / cerebrospinal fluid
  • Interferon-beta / therapeutic use
  • Longitudinal Studies
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Nervous System Diseases / blood
  • Nervous System Diseases / cerebrospinal fluid

Substances

  • Apolipoproteins
  • Biomarkers
  • Cholesterol, HDL
  • Interferon-beta