title: Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis.
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.
authors: Multiple Sclerosis Research Center of New York, USA.
authors: Violaine K
authors: VK
authors: Harris
authors: Nicola
authors: N
authors: Donelan
authors: Qi Jiang
authors: QJ
authors: Yan
authors: Kristi
authors: K
authors: Clark
authors: Amir
authors: A
authors: Touray
authors: Mustapha
authors: M
authors: Rammal
authors: Saud A
authors: SA
authors: Sadiq
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060749:alpha-2-HS-Glycoprotein / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D060749:alpha-2-HS-Glycoprotein
keywords: biomarkers; cerebrospinal fluid; fetuin-A; multiple sclerosis; natalizumab