Proteomic predictors of physical, cognitive and imaging outcomes in multiple sclerosis: 5-year follow-up study

BackgroundA quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis and supplement the clinical decision-making process. Materials and Methods202 persons with multiple sclerosis were enrolled in a longitudinal study with measurements at two time points with an average follow-up time of 5.4 years. Clinical measures included the Expanded Disability Status Scale, Timed 25-foot Walk, 9-Hole Peg and Symbol Digit Modalities Tests. Subjects underwent magnetic resonance imaging to determine the volumetric measures of the whole brain, gray matter, deep gray matter and lateral ventricles. Serum samples were analyzed using a custom immunoassay panel on the Olink platform and concentrations of 18 protein biomarkers were measured. Linear mixed-effects models and adjustment for multiple comparisons were performed. ResultsSubjects had a significant 55.6% increase in Chemokine Ligand 20 (9.7pg/mL vs. 15.1pg/mL, p<0.001) and Neurofilament light polypeptide (10.5 pg/ml vs. 11.5 pg/ml, p=0.003) at the follow-up time point. Additional changes in CUB domain-containing protein 1, Contactin 2, Glial fibrillary acidic protein, Myelin oligodendrocyte glycoprotein, and Osteopontin were noted but did not survive multiple comparisons correction. Worse clinical performance in the 9-HPT was associated with Neurofilament light polypeptide (p=0.001). Increases in several biomarker candidates were correlated with greater neurodegenerative changes as measured by different brain volumes. ConclusionMultiple proteins representing diverse biological pathways (neuroinflammation, immune modulation, and neuroaxonal integrity) associate with physical, cognitive and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care.