Proteomic signatures of physical, cognitive, and imaging outcomes in multiple sclerosis

Abstract

BackgroundA quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision‐making process.Materials and MethodsIn total, 202 PwMS 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 (9.7 pg/mL vs. 15.1 pg/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 comparison 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, selected from a disease activity test that represent diverse biological pathways, are associated with physical, cognitive, and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care.

Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis

“…Our results from serum biomarkers are supported by recent reports showing that higher blood MOG levels are associated with more severe clinical disease, worse cognitive function, and a higher burden of structural damage in MRI of PwMS. 46 Similarly, blood GFAP concentration could reflect and predict disease progression in PwMS, 47 highlighting the pathological role of astrocytes in disease progression. This aligns with translational work showing that astrocytes are involved in neurotoxicity, synaptic degeneration, 48 and dendrite removal during cell death.…”