title: Vitamin D Binding Protein Isoforms and Apolipoprotein E in Cerebrospinal Fluid as Prognostic Biomarkers of Multiple Sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a heterogeneous and unpredictable course. To date there are no prognostic biomarkers even if they would be extremely useful for early patient intervention with personalized therapies. In this context, the analysis of inter-individual differences in cerebrospinal fluid (CSF) proteome may lead to the discovery of biological markers that are able to distinguish the various clinical forms at diagnosis.
  
  
  METHODS
  To this aim, a two dimensional electrophoresis (2-DE) study was carried out on individual CSF samples from 24 untreated women who underwent lumbar puncture (LP) for suspected MS. The patients were clinically monitored for 5 years and then classified according to the degree of disease aggressiveness and the disease-modifying therapies prescribed during follow up.
  
  
  RESULTS
  The hierarchical cluster analysis of 2-DE dataset revealed three protein spots which were identified by means of mass spectrometry as Apolipoprotein E (ApoE) and two isoforms of vitamin D binding protein (DBP). These three protein spots enabled us to subdivide the patients into subgroups correlated with clinical classification (MS aggressive forms identification: 80%). In particular, we observed an opposite trend of values for the two protein spots corresponding to different DBP isoforms suggesting a role of a post-translational modification rather than the total protein content in patient categorization.
  
  
  CONCLUSIONS
  These findings proved to be very interesting and innovative and may be developed as new candidate prognostic biomarkers of MS aggressiveness, if confirmed.
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), c/o San Luigi University Hospital, Orbassano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Perga
authors.affiliation: ABLE Biosciences, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy; LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giuliano Albo
authors.affiliation: LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lis
authors.affiliation: LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Minari
authors.affiliation: ABLE Biosciences, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy; LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Falvo
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), c/o San Luigi University Hospital, Orbassano, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marnetto
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), c/o San Luigi University Hospital, Orbassano, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Caldano
authors.affiliation: ABLE Biosciences, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy; LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Reviglione
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Berchialla
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Capobianco
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Malentacchi
authors.affiliation: ABLE Biosciences, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy; LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Corpillo
authors.affiliation: Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), c/o San Luigi University Hospital, Orbassano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015153:Blotting, Western; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000145:classification / Q000175:diagnosis; D011379:Prognosis; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D020543:Proteome / Q000145:classification / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D014809:Vitamin D-Binding Protein / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D020033:Protein Isoforms; D020543:Proteome; D014809:Vitamin D-Binding Protein