Protein biomarkers for multiple sclerosis: semi-quantitative analysis of cerebrospinal fluid candidate protein biomarkers in different forms of multiple sclerosis

Mult Scler. 2012 Aug;18(8):1081-91. doi: 10.1177/1352458511433303. Epub 2012 Jan 17.

Abstract

Background: The complex pathogenesis of multiple sclerosis, combined with an unpredictable prognosis, requires identification of disease-specific diagnostic and prognostic biomarkers.

Objective: To determine whether inflammatory proteins, such as neurofilament light chain, myelin oligodendrocyte glycoprotein and myelin basic protein, and neurodegenerative proteins, such as tau and glial fibrillary acidic protein, can serve as biomarkers for predicting the clinical subtype and prognosis of MS.

Methods: Cerebrospinal fluid and serum samples were collected from patients with a diagnosis of clinically isolated syndrome (n = 46), relapsing-remitting MS (n = 67) or primary-progressive MS (n = 22) along with controls having other non-inflammatory neurological disease (n = 22). Western blot analyses were performed for the listed proteins. Protein levels were compared among different clinical subtypes using one-way analysis of variance analysis. The k-nearest neighbour algorithm was further used to assess the predictive use of these proteins for clinical subtype classification.

Results: The results showed that each of tau, GFAP, MOG and NFL protein concentrations differed significantly (p < 0.001) in multiple sclerosis clinical subtypes compared with the controls. Levels of the proteins also differed between the multiple sclerosis clinical subtypes, which may be associated with the underlying disease process. Classification studies revealed that these proteins might be useful for identifying multiple sclerosis clinical subtypes.

Conclusions: We showed that select biomarkers may have potential in identifying multiple sclerosis clinical subtypes. We also showed that the predictive value of the prognosis increased when using a combination of the proteins versus using them individually.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Blotting, Western
  • Case-Control Studies
  • Cerebrospinal Fluid Proteins / analysis*
  • Cerebrospinal Fluid Proteins / blood
  • Demyelinating Diseases / blood
  • Demyelinating Diseases / cerebrospinal fluid
  • Demyelinating Diseases / diagnosis*
  • Diagnosis, Differential
  • Glial Fibrillary Acidic Protein / blood
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / diagnosis*
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis*
  • Myelin-Oligodendrocyte Glycoprotein / blood
  • Myelin-Oligodendrocyte Glycoprotein / cerebrospinal fluid
  • Neurofilament Proteins / blood
  • Neurofilament Proteins / cerebrospinal fluid
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Turkey
  • Young Adult
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid

Substances

  • Biomarkers
  • Cerebrospinal Fluid Proteins
  • Glial Fibrillary Acidic Protein
  • MAPT protein, human
  • MOG protein, human
  • Myelin-Oligodendrocyte Glycoprotein
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins