Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis |
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Authors: | Ann C Kroksveen Jacob D Jaffe Elise Aasebø Harald Barsnes Yngvild Bjørlykke Diego Franciotta Hasmik Keshishian Kjell‐Morten Myhr Jill A Opsahl Vincent van Pesch Charlotte E Teunissen Øivind Torkildsen Rune J Ulvik Heidrun Vethe Steven A Carr Frode S Berven |
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Institution: | 1. The KG Jebsen Centre for MS‐research, Department of Clinical Medicine, University of Bergen, Bergen, Norway;2. Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway;3. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA;4. Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway;5. Department of Clinical Science, University of Bergen, Bergen, Norway;6. Laboratory of Neuroimmunology, “C. Mondino” National Neurological Institute, Pavia, Italy;7. The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway;8. Neurochemistry Unit, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;9. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands;10. Department of Clinical Medicine, University of Bergen, Bergen, Norway;11. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway |
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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. |
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Keywords: | Biomarkers Biomedicine Cerebrospinal fluid Multiple sclerosis Quantitative mass spectrometry Secretogranin‐1 |
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