Cerebrospinal fluid proteome profile in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis

• Published in: Multiple sclerosis 2008-09, Vol.14, p.S290-S290
• Main Authors: Tumani, H, Rau, D, Palm, C, Brettschneider, J, Suessmuth, S, Lehmensiek, V
• Format: Article
• Language: English
• ISSN: 1352-4585

Background: Proteome analysis of cerebrospinal fluid (CSF) could be a useful diagnostic tool to identify candidate biomarkers in patients with clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS). Objective: To compare the CSF proteome profile of patients with (a) RRMS, (b) CIS who will remain with CIS, and (c) CIS who will develop a second relapse within a follow-up time of 2 years (CIS-RRMS). Methods: Pooled CSF samples of n=8 patients with RRMS, n=8 patients with CIS and n=8 patients CIS-RRMS were studied using 2-dimensional difference in gel electrophoresis (2-D-DIGE) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Spots with significantly different volumes were selected for protein identification and further validation studies using immunoassays. Results: In the first set of analysis 23 spots corresponding to 13 distinct proteins could be identified to be significantly downregulated in patients with CIS when compared with patients with RRMS. Five proteins were found to be significantly upregulated. In the second set of analyses comparing patients with CIS and CIS-RRMS, 22 spots corresponding to 13 distinct proteins were found to be significantly different, 2 of which were downregulated, whereas 11 proteins were upregulated in patients remaining with CIS after 2 years. 2-D-DIGE results of two of the identified proteins (alpha-2-HS-glycoprotein, proapolipoprotein) were confirmed by Western blot analysis. Conclusions: 2-D-DIGE is a promising semi-quantitative tool to compare the CSF proteome profile of patients with CIS and RRMS. The diagnostic relevance of the candidate biomarker proteins identified so far are currently validated by quantitative immunoassays in conjunction with blood-CSF barrier related evaluation.