Author Of 1 Presentation
P0088 - Identification of putative multiple sclerosis biomarkers in CSF by targeted-mass spectrometry (ID 913)
Abstract
Background
The individual expression of Multiple Sclerosis (MS) is highly heterogeneous. One of the greatest potential benefits of biomarkers is to predict disease severity and guide therapeutic choices.
Objectives
Our objective is to evaluate the predictive value of soluble brain-specific proteins of 10-year MS clinical outcomes.
Methods
This retrospective study analyzed cerebrospinal fluid (CSF) from 35 MS patients (mean age: 42; 79% female) and 23 non-MS controls (mean age: 35.5; 68% female) collected within 5 years of disease onset. We quantified 63 brain-specific proteins in the CSF of these patients using a targeted liquid-chromatography tandem mass spectrometry assay. This assay was previously developed in-house by mining of the Human Protein Atlas database and experimental search of CSF to establish brain-enriched proteins.
Results
Our parallel reaction monitoring assay (PRM) used in this study had high assay reproducibility (median across peptides CV = 5.7%). Twelve proteins significantly differentiated MS from controls (p<0.05). The levels of 6 proteins at baseline were significantly associated with CIS, RRMS or PPMS. We also observed a trend with a number of proteins negatively predicting evolution of CIS to RRMS or SPMS. Finally, we observed an association between 3 proteins and the rate of EDSS progression rate over 10 years (Spearman rank correlation: r=-0.59, r=-0.36, r=-0.44; p=0.0006, p=0.046, p=0.0151 respectively).
Conclusions
We identified 12 CSF brain-specific proteins that are unique to MS patients and 3 proteins that seem to predict disease course over the next decade. These proteins also highlight putative pathways implicated in MS pathogenesis and can be targets for future therapeutic regimes.