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

In the present study, we aimed to discover cerebrospinal fluid (CSF) proteins with significant abundance difference between early multiple sclerosis patients and controls, and do an initial verification of these proteins using selected reaction monitoring (SRM). iTRAQ and Orbitrap MS were used to compare the CSF proteome of patients with clinically isolated syndrome (CIS) (n = 5), patients with relapsing–remitting multiple sclerosis that had CIS at the time of lumbar puncture (n = 5), and controls with other inflammatory neurological disease (n = 5). Of more than 1200 identified proteins, five proteins were identified with significant abundance difference between the patients and controls. In the initial verification using SRM we analyzed a larger patient and control cohort (n = 132) and also included proteins reported as differentially abundant in multiple sclerosis in the literature. We found significant abundance difference for 11 proteins after verification, of which the five proteins alpha-1-antichymotrypsin, contactin-1, apolipoprotein D, clusterin, and kallikrein-6 were significantly differentially abundant in several of the group comparisons. This initial study form the basis for further biomarker verification studies in even larger sample cohorts, to determine if these proteins have relevance as diagnostic or prognostic biomarkers for multiple sclerosis.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (170 K)Download as PowerPoint slideHighlights► We compared the CSF proteome of MS patients and controls with quantitative proteomics. ► We used SRM to verify differentially abundant proteins in 132 patients and controls. ► We included MS-related literature derived proteins for SRM analysis. ► This is to date the largest SRM study of differentially abundant proteins in MS.