CSF proteome analysis in clinically isolated syndrome (CIS): Candidate markers for conversion to definite multiple sclerosis

Cerebrospinal fluid (CSF) is a promising source of biomarkers in clinically isolated syndrome (CIS), which frequently presents as a first episode of multiple sclerosis (MS). Using the two-dimensional difference in gel electrophoresis (2-D DIGE), we compared CSF samples from patients with CIS that remained CIS (CIS-CIS, n = 8) over a follow-up time of 2 years and from patients with CIS that developed definite MS of the relapsing-remitting subtype (CIS-RRMS, n = 8) over the same period. Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots ELISA experiments were performed. We identified one protein that was upregulated in CIS-RRMS (serin peptidase inhibitor) and eight proteins (alpha-1-B-glycoprotein, Fetuin-A, apolipoprotein A4, haptoglobin, human Zinc-alpha-2-glycoprotein (ZAG), Retinol-binding protein, superoxid dismutase 1, transferrin) that were down-regulated in CIS-RRMS vs. CIS-CIS. For Fetuin-A, our findings could be confirmed by ELISA. The pathophysiological role as well as clinical relevance of these candidate proteins in CIS remains to be further clarified by future studies.