Cerebrospinal fluid proteome profile in multiple sclerosis

Abstract

Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.

The emerging role of vitamin D binding protein in multiple sclerosis

“…Using two-dimensional difference gel electrophoresis (2-D-DIGE) and MALDI-TOF Mass Spectrometry, Lehmensiek et al [25] have shown a decreased concentration of DBP in the CSF taken during an acute relapse from 12 CIS but not from 12 RRMS cases compared to other neurological diseases (OND). However, another study by Qin et al [33] has shown lower DBP levels in the CSF of 10 RRMS patients at the time of a relapse compared to 10 OND individuals, again using 2D-DIGE and MALDI-TOF Mass Spectrometry.…”

Discovery of Novel Disease-specific and Membrane-associated Candidate Markers in a Mouse Model of Multiple Sclerosis

“…Differential gene and protein expression profiles have been generated based on comparative analyses of healthy control and disease-affected tissues derived from clinical samples (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and animal models (19 -29). These biomarker discovery platforms include gel-based approaches such as two-dimensional gel electrophoresis (2D-GE) (10,17,30), 2D-difference image gel electrophoresis (2D-DIGE) (9,14), as well as shotgun proteomics techniques (11,13,16,31,32) incorporating the use of label-free or stable isotope labeling LC-MS-based strategies for quantitative proteomic studies. In recent years there has been exponential growth in the use of these alternative gel-free shotgun proteomics strategies, which has been facilitated by advances in mass spectrometry instrumentation and computational capabilities.…”

Acute‐phase proteins investigation based on lectins affinity capture prior to 2‐DE separation: Application to serum from multiple sclerosis patients

“…Although it is generally classified as a tuner of the immune response, its up-regulation was already shown in pediatric MS [40] and it was discovered to trigger neuronal degeneration [49]. Transferrin is an ironbinding protein reported to be down-regulated in CSF and linked to CIS-MS conversion [44,50]. This could be explained considering its multiple roles on iron metabolism that could affect the formation of myelin sheath, the neurotransmitters synthesis and the oxidative phosphorylation.…”

“…Vitamin D-binding protein acts as a carrier protein for vitamin D and its plasma metabolites, and also serves as a scavenger to clear endotoxins and extracellular G-actin released from necrotic cells. Vitamin D-binding protein has also the capacity to respond in case of acute tissue injury becoming a macrophage-activating factor, a neutrophils chemo-attractant and a C5a-mediated signaling enhancer [40,50,51]. Finally, complement 3 chain C is a degradation product of C3 factor of the complement system, a signal of its activation in the considered district in the presence of a type II or cytotoxic hyper-sensibility.…”

“…Finally, complement 3 chain C is a degradation product of C3 factor of the complement system, a signal of its activation in the considered district in the presence of a type II or cytotoxic hyper-sensibility. Complement 3 chain C has been already correlated to MS [50,52] and its intrathecal concentrations used as a parameter to discriminate between infectious or autoimmune neurological diseases [53].…”