Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.
References
[1]
Anderson, N.L.; Anderson, N.G. Proteome and proteomics: New technologies, new concepts, and new words. Electrophoresis 1998, 19, 1853–1861.
[2]
Gygi, S.P.; Aebersold, R. Mass spectrometry and proteomics. Curr. Opin. Chem. Biol 2000, 4, 489–494.
[3]
Gygi, S.P.; Corthals, G.L.; Zhang, Y.; Rochon, Y.; Aebersold, R. Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc. Natl. Acad. Sci. USA 2000, 97, 9390–9395.
Calvo, K.R.; Liotta, L.A.; Petricoin, E.F. Clinical proteomics: From biomarker discovery and cell signaling profiles to individualized personal therapy. Biosci. Rep 2005, 25, 107–125.
[6]
Brancia, F.L. Mass spectrometry based strategies in quantitative proteomics. Curr. Anal. Chem 2006, 2, 1–7.
[7]
Ross, P.L.; Huang, Y.N.; Marchese, J.N.; Williamson, B.; Parker, K.; Hattan, S.; Khainovski, N.; Pillai, S.; Dey, S.; Daniels, S.; et al. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol. Cell. Proteomics 2004, 3, 1154–1169.
[8]
Hanrieder, J.; Nyakas, A.; Naessen, T.; Bergquist, J. Proteomic analysis of human follicular fluid using an alternative bottom-up approach. J. Proteome Res 2008, 7, 443–449.
[9]
UniProt Home Page, Available online: http://www.uniprot.org , accessed on 6 January 2012.
Stoop, M.P.; Singh, V.; Dekker, L.J.; Titulaer, M.K.; Stingl, C.; Burgers, P.C.; Sillevis Smitt, P.A.; Hintzen, R.Q.; Luider, T.M. Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis. PLoS One 2010, 5, doi:10.1371/journal.pone.0012442.
[16]
Ottervald, J.; Franzen, B.; Nilsson, K.; Andersson, L.I.; Khademi, M.; Eriksson, B.; Kjellstrom, S.; Marko-Varga, G.; Vegvari, A.; Harris, R.A.; et al. Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers. J. Proteomics 2010, 73, 1117–1132.
[17]
Cantorna, M.T.; Mahon, B.D. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp. Biol. Med. (Maywood) 2004, 229, 1136–1142.
[18]
Raghuwanshi, A.; Joshi, S.S.; Christakos, S. Vitamin D and multiple sclerosis. J. Cell. Biochem 2008, 105, 338–343.
[19]
Myhr, K.M. Vitamin D treatment in multiple sclerosis. J. Neurol. Sci 2009, 286, 104–108.
[20]
Adams, R.A.; Bauer, J.; Flick, M.J.; Sikorski, S.L.; Nuriel, T.; Lassmann, H.; Degen, J.L.; Akassoglou, K. The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J. Exp. Med 2007, 204, 571–582.
[21]
Ristori, G.; Laurenti, F.; Stacchini, P.; Gasperini, C.; Buttinelli, C.; Pozzilli, C.; Salvetti, M. Serum amyloid A protein is elevated in relapsing-remitting multiple sclerosis. J. Neuroimmunol 1998, 88, 9–12.
[22]
Boylan, M.T.; Crockard, A.D.; Duddy, M.E.; Armstrong, M.A.; McMillan, S.A.; Hawkins, S.A. Interferon-beta1a administration results in a transient increase of serum amyloid A protein and C-reactive protein: Comparison with other markers of inflammation. Immunol. Lett 2001, 75, 191–197.
[23]
Lucchinetti, C.F.; Bruck, W.; Rodriguez, M.; Lassmann, H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 1996, 6, 259–274.
[24]
Mahad, D.; Ziabreva, I.; Lassmann, H.; Turnbull, D. Mitochondrial defects in acute multiple sclerosis lesions. Brain 2008, 131, 1722–1735.
[25]
McDonald, W.I.; Compston, A.; Edan, G.; Goodkin, D.; Hartung, H.P.; Lublin, F.D.; McFarland, H.F.; Paty, D.W.; Polman, C.H.; Reingold, S.C.; et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol 2001, 50, 121–127.
[26]
Kurtzke, J.F. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 1983, 33, 1444–1452.
[27]
Hanrieder, J.; Wetterhall, M.; Enblad, P.; Hillered, L.; Bergquist, J. Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates. J. Neurosci. Methods 2009, 177, 469–478.
[28]
Abdi, F.; Quinn, J.; Jankovic, J.; McIntosh, M.; Leverenz, J.; Peskind, E. Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J. Alzheimers Dis 2006, 9, 293–348.
[29]
Andersson, M.; Alvarez-Cermeno, J.; Bernardi, G.; Cogato, I.; Fredman, P.; Frederiksen, J.; Fredrikson, S.; Gallo, P.; Grimaldi, L.M.; Gronning, M.; et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report. J. Neurol. Neurosurg Psychiatry 1994, 57, 897–902.
[30]
Bergquist, J. FTICR mass spectrometry in proteomics. Curr. Opin. Mol. Ther 2003, 5, 310–314.
[31]
Ramstrom, M.; Palmblad, M.; Markides, K.E.; Hakansson, P.; Bergquist, J. Protein identification in cerebrospinal fluid using packed capillary liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry. Proteomics 2003, 3, 184–190.
[32]
Ramstrom, M.; Ivonin, I.; Johansson, A.; Askmark, H.; Markides, K.E.; Zubarev, R.; Hakansson, P.; Aquilonius, S.M.; Bergquist, J. Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. Proteomics 2004, 4, 4010–4018.
