title: Identification of biomarkers for diagnosis and progression of MS by MALDI-TOF mass spectrometry.
abstract: BACKGROUND
  Body fluid biomarkers for clinical subtyping and monitoring of disease progression are of considerable interest in multiple sclerosis (MS). Proteomics tools are optimal for the unbiased simultaneous detection of large series of peptides and proteins.
  
  
  OBJECTIVE
  To identify novel candidate biomarkers discriminating patients with MS from patients with other neurological diseases (OND), and for subtyping of relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) MS patients using a high-throughput MALDI-TOF-based mass spectrometry method.
  
  
  METHODS
  Paired cerebrospinal fluid (CSF) and serum samples of 41 RRMS, 30 SPMS, 13 PPMS patients and 25 patients with OND were analysed.
  
  
  RESULTS
  Out of a total of 100 detected peptides in CSF and 200 peptides in serum, 11 peptides were differentially regulated in serum and two in CSF between patients with MS and the OND control group. Eleven peptides were differentially regulated in both serum and CSF between relapse-onset MS and PPMS patients. Lastly, four peptides were differentially regulated in serum and two in CSF between RRMS and SPMS patients. Specific peaks regulated in MS were tentatively identified as fragments of secretogranin III and complement C3. The peak intensity of the CSF peptide ion with m/z value 8607.7 correlated to atrophy (r = -0.27, p < 0.005), black hole volumes (r = 0.31, p < 0.008) and total lesion load (r = 0.34, p < 0.003). A serum peptide with m/z value of 872.4 elevated in SPMS correlated to Expanded Disability Status Scale (r = 0.341, p < 0.005) and atrophy (r = -0.286, p < 0.028).
  
  
  CONCLUSIONS
  Using high-throughput body fluid profiling by MALDI-TOF mass spectrometry, small proteins and peptides were detected as promising candidate biomarkers for diagnosis and disease progression of MS.
authors.affiliation: NUBIN, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. c.teunissen@vumc.nl
authors.forename: C E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: M J A
authors.initials: MJ
authors.lastname: Koel-Simmelink
authors.forename: T V
authors.initials: TV
authors.lastname: Pham
authors.forename: J C
authors.initials: JC
authors.lastname: Knol
authors.forename: M
authors.initials: M
authors.lastname: Khalil
authors.forename: A
authors.initials: A
authors.lastname: Trentini
authors.forename: J
authors.initials: J
authors.lastname: Killestein
authors.forename: J
authors.initials: J
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Vrenken
authors.forename: V
authors.initials: V
authors.lastname: Popescu
authors.forename: C D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: C R
authors.initials: CR
authors.lastname: Jimenez
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001284:Atrophy; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001798:Blood Proteins / Q000032:analysis; D001921:Brain / Q000473:pathology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D009426:Netherlands; D011237:Predictive Value of Tests; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D002556:Cerebrospinal Fluid Proteins