Multiple sclerosis‐related proteins identified in cerebrospinal fluid by advanced mass spectrometry

Abstract

A total of 164 cerebrospinal fluid (CSF) samples taken from neurological patients were classed into four groups according to the clinical diagnosis: multiple sclerosis (MScl, n = 44), clinically isolated syndrome of demyelination (CIS, n = 40), other inflammatory neurological disease (OIND, n = 26) and other neurological disease (OND, n = 54). After tryptic digestion, the samples were measured by MALDI-TOF MS. Spectra were analyzed using the R-project software package, in which a peak detection algorithm was developed. Subsequently, the peak lists were compared based on ranked data (non-parametric). Significant differences were observed in the comparisons of MScl vs. OND and CIS vs. OND. The comparisons of MScl vs. OIND, and CIS vs. OIND showed fewer significant differences. No significant differences were found in comparisons MScl vs. CIS and OIND vs. OND. MScl and CIS had strikingly similar profiles, probably a reflection of common pathological mechanisms. Three differentially expressed proteins in the comparison of MScl vs. OND were identified: chromogranin A, a potential marker for neurodegeneration; and two important factors in complement-mediated inflammatory reaction, clusterin and complement C3. CSF chromogranin A levels were confirmed to be significantly elevated in the MScl group using an ELISA.

Discovery and initial verification of differentially abundant proteins between multiple sclerosis patients and controls using iTRAQ and SID-SRM

“…Since PPMS and healthy controls were not included for SRM verification, our study is not comparable to this study from Stoop and colleagues. However, the same group have also reported increased abundance of apo D in CIS compared to OIND [48], but we did not find this abundance difference using SRM (Supplementary Table 6). A possible explanation for the discrepancy, may be that that we monitored the abundance of apo D based on the peptide NILTSNNIDVK, and differential abundance for the RRMS/PPMS and CIS patients were reported for NPNLPPETVDSLK and VLNQELR, respectively.…”

Neurofilaments as biomarkers in multiple sclerosis

“…This has led to promising biomarkers such as vitamin D-binding protein, jagged-1, contactin-1, fetuin-A, angiotensinogen and chitinase 3-like proteins. [34][35][36] Studies addressing disease progression, defined as disability development in established MS, show promising results for the presence of CSF oligoclonal band IgM, which predict a worse disease course on follow-up in relapse-onset MS patients. 37 These results are in agreement with earlier reports showing that the presence of lipid-specific immunoglobulin M bands in CSF was associated with reduced time to conversion to a SPMS course and to reaching an EDSS score of four whilst the presence of IgM in CSF has prognostic value in CIS patients.…”

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.…”