Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis

Mol Cell Proteomics. 2016 Jan;15(1):318-28. doi: 10.1074/mcp.M115.053256. Epub 2015 Nov 9.

Abstract

Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-β-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / cerebrospinal fluid
  • Amino Acid Sequence
  • Chitinase-3-Like Protein 1
  • Diagnosis, Differential
  • Dipeptidases / cerebrospinal fluid
  • Disease Progression
  • Humans
  • Lectins / cerebrospinal fluid
  • Mass Spectrometry / methods
  • Molecular Sequence Data
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / metabolism*
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / metabolism*
  • Peptides / cerebrospinal fluid
  • Peptides / metabolism
  • Prognosis
  • Proteome / classification
  • Proteome / metabolism*
  • Proteomics / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Syndrome

Substances

  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • Peptides
  • Proteome
  • Dipeptidases
  • dipeptidase