title: Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.
abstract: The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.
authors.affiliation: National Research Council of Italy, Institute for Biomedical Technologies, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Liguori
authors.affiliation: National Research Council of Italy, Institute of Neurological Sciences, Mangone (CS), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Qualtieri
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Tortorella
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Vita
authors.initials: V
authors.lastname: Direnzo
authors.affiliation: National Research Council of Italy, Institute of Neurological Sciences, Mangone (CS), Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Bagalà
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Mastrapasqua
authors.affiliation: National Research Council of Italy, Institute of Neurological Sciences, Mangone (CS), Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Spadafora
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005340:Fibrinogen / Q000134:cerebrospinal fluid*; D005344:Fibrinopeptide A / Q000134:cerebrospinal fluid*; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D005344:Fibrinopeptide A; D005340:Fibrinogen
references.citation: Acta Neurol Scand. 2013 May;127(5):301-8
references.pmid: 22970985
references.citation: PLoS One. 2010 Aug 27;5(8):e12442
references.pmid: 20805994
references.citation: Mult Scler. 2013 Jul;19(8):1074-83
references.pmid: 23234810
references.citation: Expert Rev Proteomics. 2010 Dec;7(6):907-17
references.pmid: 21142891
references.citation: Neurology. 1996 Apr;46(4):907-11
references.pmid: 8780061
references.citation: Neurology. 2014 Feb 25;82(8):681-90
references.pmid: 24453076
references.citation: Nat Commun. 2012;3:1227
references.pmid: 23187627
references.citation: Neuro Endocrinol Lett. 2008 Dec;29(6):971-6
references.pmid: 19112391
references.citation: J Biol Chem. 2013 Jan 11;288(2):1114-24
references.pmid: 23172224
references.citation: Neurol Clin. 2011 May;29(2):309-21
references.pmid: 21439443
references.citation: Brain. 2010 Apr;133(Pt 4):1082-93
references.pmid: 20237129
references.citation: Ann Neurol. 1983 Mar;13(3):227-31
references.pmid: 6847134
references.citation: J Int Med Res. 2011;39(6):2402-13
references.pmid: 22289560
references.citation: Neurology. 2009 Dec 1;73(22):1914-22
references.pmid: 19949037
references.citation: Ann Neurol. 2012 May;71(5):614-23
references.pmid: 22522477
references.citation: J Cell Sci. 2009 Nov 15;122(Pt 22):4195-207
references.pmid: 19861493
references.citation: Ann Neurol. 2005 Dec;58(6):840-6
references.pmid: 16283615
references.citation: Neuroscience. 2009 Dec 29;164(4):1887-93
references.pmid: 19782721
references.citation: Anal Biochem. 2010 Jul 1;402(1):13-9
references.pmid: 20346905
references.citation: Ann N Y Acad Sci. 2012 Oct;1269:110-6
references.pmid: 23045978
references.citation: J Alzheimers Dis. 2010;20(4):1039-49
references.pmid: 20413871
references.citation: Ann Neurol. 2011 Feb;69(2):292-302
references.pmid: 21387374
references.citation: Curr Protein Pept Sci. 2005 Aug;6(4):373-85
references.pmid: 16101435
references.citation: Lancet Neurol. 2012 Apr;11(4):349-60
references.pmid: 22441196
references.citation: J Neurol Neurosurg Psychiatry. 2011 Dec;82(12):1355-9
references.pmid: 21622936
references.citation: Arch Neurol. 2012 Jul;69(7):868-72
references.pmid: 22431836
references.citation: Brain. 2014 Feb;137(Pt 2):433-48
references.pmid: 24355709
references.citation: Nature. 2011 Aug 10;476(7359):214-9
references.pmid: 21833088
references.citation: Ann Neurol. 2001 Jul;50(1):121-7
references.pmid: 11456302
references.citation: Proteomics Clin Appl. 2013 Jan;7(1-2):91-108
references.pmid: 23112123
references.citation: PLoS One. 2013 Sep 10;8(9):e66117
references.pmid: 24039694
references.citation: J Neurol. 2005 Sep;252 Suppl 3:iii21-iii27
references.pmid: 16170496
references.citation: Mult Scler. 2011 Jul;17(7):838-50
references.pmid: 21505015
references.citation: Ann Neurol. 2011 Dec;70(6):897-912
references.pmid: 22190364
references.citation: J Clin Epidemiol. 2001 Apr;54(4):343-9
references.pmid: 11297884
references.citation: Ann Neurol. 2012 May;71(5):601-13
references.pmid: 22473675
references.citation: Mol Med. 2011 May-Jun;17(5-6):568-73
references.pmid: 21210072
references.citation: Brain. 2001 Oct;124(Pt 10):1978-88
references.pmid: 11571216
references.citation: J Neurochem. 2007 Dec;103(5):1932-9
references.pmid: 17953655
references.citation: Mult Scler. 2014 Feb;20(2):234-42
references.pmid: 23842212
references.citation: Mult Scler. 2013 Oct;19(12):1679-80
references.pmid: 23828870
references.citation: J Neurol Neurosurg Psychiatry. 2014 Jan;85(1):67-75
references.pmid: 23486991
references.citation: Trends Mol Med. 2001 Mar;7(3):115-21
references.pmid: 11286782
references.citation: Mult Scler. 2013 Nov;19(13):1802-9
references.pmid: 23695446