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Vitamin D Binding Protein Isoforms and Apolipoprotein E in Cerebrospinal Fluid as Prognostic Biomarkers of Multiple Sclerosis


Simona Perga1,4☯*, Alessandra Giuliano Albo2,3☯, Katarzyna Lis3, Nicoletta Minari3, Sara Falvo2,3, Fabiana Marnetto1,4, Marzia Caldano1,4, Raffaella Reviglione2,3, Paola Berchialla5, Marco A. Capobianco1, Maria Malentacchi1, Davide Corpillo2,3, Antonio Bertolotto1,4

1 Neurology Unit 2 & Regional Referral Multiple Sclerosis Centre (CReSM), San Luigi University Hospital, Orbassano, Italy,
2 ABLE Biosciences, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy,
3 LIMA, Bioindustry Park Silvano Fumero SpA, Colleretto Giacosa, Italy,
4 Neuroscience Institute Cavalieri Ottolenghi (NICO), c/o San Luigi University Hospital, Orbassano, Italy,
5 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

PLOS ONE | DOI:10.1371/journal.pone.0129291 June 5, 2015



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.


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.


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.

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