Identification of markers of relapse in EAE using high-resolution quantitative mass spectrometry

Abstract

Abstract Approximately 85 percent of individuals newly diagnosed with multiple sclerosis have the relapsing-remitting form of the disease characterized by attacks of neurologic symptoms that are unpredictable in occurrence and duration. Currently there are no clinically available biomarkers predictive of relapse. To address this need, we investigated CNS proteome changes over the disease course of relapsing-remitting experimental autoimmune encephalomyelitis (EAE) in SJL mice as a preclinical model of the disease. Using a high-throughput quantitative preparation technique and high-resolution Bruker timsTOF mass spectrometry, we were able to identify thousands of unique proteins at each disease timepoint. Principal component analysis of protein expression confirmed that the remission and relapse phases of disease cluster independently, indicating distinguishable variation in protein expression profiles between the two disease states. Importantly, statistical testing identified proteins with differential expression in the CNS at different stages of disease, several of which are CNS specific. We are seeking to detect corollary changes in these CNS-specific proteins in the serum, pointing to a minimally invasive means of monitoring disease progress and measuring drug efficacy. Our study will validate homologous human biomarkers to guide treatment in individual patients and allow for proactive therapeutic intervention. Furthermore, our results may provide insights into mechanisms that contribute to disease pathology and offer novel therapeutic targets.