Sulfatide isoform pattern in cerebrospinal fluid discriminates progressive MS from relapsing-remitting MS

J Neurochem. 2018 Aug;146(3):322-332. doi: 10.1111/jnc.14452. Epub 2018 Jul 3.

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype of MS and might play a role in the progression of the disease.

Keywords: axonal loss; biomarkers; cerebrospinal fluid; demyelination; inflammation; mass spectrometry; multiple sclerosis; sulfatide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / cerebrospinal fluid
  • Disease Progression
  • Female
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid*
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis*
  • Neurofilament Proteins / cerebrospinal fluid
  • Principal Component Analysis
  • Protein Isoforms / cerebrospinal fluid
  • ROC Curve
  • Sulfoglycosphingolipids / cerebrospinal fluid*
  • Sulfoglycosphingolipids / chemistry
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Neurofilament Proteins
  • Protein Isoforms
  • Sulfoglycosphingolipids
  • neurofilament protein L