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.
Tumani
H
H
Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. hayrettin.tumani@uni-ulm.de
Lehmensiek
V
V
Rau
D
D
Guttmann
I
I
Tauscher
G
G
Mogel
H
H
Palm
C
C
Hirt
V
V
Suessmuth
S D
SD
Sapunova-Meier
I
I
Ludolph
A C
AC
Brettschneider
J
J
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis / Q000378:metabolism; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis / Q000134:cerebrospinal fluid; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D020543:Proteome; C109149:SPINT1 protein, human