Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis

Mult Scler. 2013 Oct;19(11):1462-72. doi: 10.1177/1352458513477923. Epub 2013 Feb 25.

Abstract

Background: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways.

Objective: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity.

Methods: We measured fetuin-A in CSF and plasma of patients with MS and correlated these findings to clinical disease activity and natalizumab response. Fetuin-A expression was characterized in MS brain tissue and in experimental autoimmune encephalomyelitis (EAE) mice. We also examined the pathogenic role of fetuin-A in EAE using fetuin-A-deficient mice.

Results: Elevated CSF fetuin-A correlated with disease activity in MS. In natalizumab-treated patients, CSF fetuin-A levels were reduced one year post-treatment, correlating with therapeutic response. Fetuin-A was markedly elevated in demyelinated lesions and in gray matter within MS brain tissue. Similarly, fetuin-A was elevated in degenerating neurons around demyelinated lesions in EAE. Fetuin-A-deficient mice demonstrated delayed onset and reduced severity of EAE symptoms.

Conclusions: Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process.

Keywords: biomarkers; cerebrospinal fluid; fetuin-A; multiple sclerosis; natalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / cerebrospinal fluid*
  • Brain / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Reverse Transcriptase Polymerase Chain Reaction
  • alpha-2-HS-Glycoprotein / cerebrospinal fluid*

Substances

  • Biomarkers
  • alpha-2-HS-Glycoprotein