Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis

Tanuja Chitnis, Ferhan Qureshi (), Victor M. Gehman, Michael Becich, Riley Bove, Bruce A. C. Cree, Refujia Gomez, Stephen L. Hauser, Roland G. Henry, Amal Katrib, Hrishikesh Lokhande, Anu Paul, Stacy J. Caillier, Adam Santaniello, Neda Sattarnezhad, Shrishti Saxena, Howard Weiner, Hajime Yano and Sergio E. Baranzini
Additional contact information
Tanuja Chitnis: Brigham and Women’s Hospital
Ferhan Qureshi: Inc
Victor M. Gehman: Inc
Michael Becich: Inc
Riley Bove: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Bruce A. C. Cree: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Refujia Gomez: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Stephen L. Hauser: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Roland G. Henry: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Amal Katrib: Inc
Hrishikesh Lokhande: Brigham and Women’s Hospital
Anu Paul: Brigham and Women’s Hospital
Stacy J. Caillier: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Adam Santaniello: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco
Neda Sattarnezhad: Brigham and Women’s Hospital
Shrishti Saxena: Brigham and Women’s Hospital
Howard Weiner: Brigham and Women’s Hospital
Hajime Yano: Brigham and Women’s Hospital
Sergio E. Baranzini: Department of Neurology. Weill Institute for Neurosciences. University of California San Francisco

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.

Date: 2024
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DOI: 10.1038/s41467-024-48602-9

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