CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes

PLoS One. 2015 May 5;10(5):e0122045. doi: 10.1371/journal.pone.0122045. eCollection 2015.

Abstract

Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Computational Biology
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Multiple Sclerosis / classification
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis, Chronic Progressive / metabolism
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • Proteomics*
  • Th17 Cells / metabolism

Grants and funding

This study was supported by the The Scientific and Technological Research Council of Turkey (TUBITAK) project number 109S070. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.