Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect disease activity in multiple sclerosis
Chitnis, T.; Qureshi, F.; Gehman, V. M.; Becich, M.; Bove, R.; Cree, B. A. C.; Gomez, R.; Hauser, S. L.; Henry, R. G.; Katrib, A.; Lokhande, H.; Paul, A.; Caillier, S. J.; Santaniello, A.; Sattarnezhad, N.; Saxena, S.; Weiner, H.; Yano, H.; Baranzini, S. E.
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Background/ObjectivesSerum proteomic analysis of deeply-phenotyped samples, biological pathway modeling and network analysis were performed to elucidate the inflammatory and neurodegenerative processes of multiple sclerosis (MS) and identify sensitive biomarkers of MS disease activity (DA). MethodsOver 1100 serum proteins were evaluated in >600 samples from three MS cohorts to identify biomarkers of clinical and radiographic (gadolinium-enhancing lesions) new MS DA. Protein levels were analyzed and associated with presence of gadolinium-enhancing lesions, clinical relapse status (CRS), and annualized relapse rate (ARR) to create a custom assay panel. ResultsTwenty proteins were associated with increased clinical and radiographic MS DA. Serum neurofilament light chain (NfL) showed the strongest univariate correlation with radiographic and clinical DA measures. Multivariate modeling significantly outperformed univariate NfL to predict gadolinium lesion activity, CRS and ARR. DiscussionThese findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA. FundingOctave Bioscience, Inc (Menlo Park, CA).
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