title: Quantitative proteomics suggests decrease in the secretogranin-1 cerebrospinal fluid levels during the disease course of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase-3-like protein 1, secretogranin-1 (Sg1), cerebellin-1, neuroserpin, cell surface glycoprotein MUC18, testican-2 and glutamate receptor 4. An independent sample set of 13 early-MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early-MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease.
authors.affiliation: The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Kroksveen
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Jaffe
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Elise
authors.initials: E
authors.lastname: Aasebø
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.|Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Barsnes
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Yngvild
authors.initials: Y
authors.lastname: Bjørlykke
authors.affiliation: Laboratory of Neuroimmunology, "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
authors.forename: Hasmik
authors.initials: H
authors.lastname: Keshishian
authors.affiliation: The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Opsahl
authors.affiliation: Neurochemistry Unit, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: van Pesch
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Torkildsen
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rune J
authors.initials: RJ
authors.lastname: Ulvik
authors.affiliation: Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Vethe
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
authors.affiliation: The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway.|The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Frode S
authors.initials: FS
authors.lastname: Berven
mesh_terms: D000328:Adult; D015415:Biomarkers; D053378:Chromogranin B / Q000134:cerebrospinal fluid* / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D040901:Proteomics
chemical_list: D015415:Biomarkers; C506134:CHGB protein, human; D053378:Chromogranin B
keywords: Biomarkers; Biomedicine; Cerebrospinal fluid; Multiple sclerosis; Quantitative mass spectrometry; Secretogranin-1