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

Serum 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). Over 1100 serum proteins were...

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Published in:medRxiv : the preprint server for health sciences
Main Authors: Chitnis, Tanuja, Qureshi, Ferhan, Gehman, Victor M, Becich, Michael, Bove, Riley, Cree, Bruce A C, Gomez, Refujia, Hauser, Stephen L, Henry, Roland G, Katrib, Amal, Lokhande, Hrishikesh, Paul, Anu, Caillier, Stacy J, Santaniello, Adam, Sattarnezhad, Neda, Saxena, Shrishti, Weiner, Howard, Yano, Hajime, Baranzini, Sergio E
Format: Journal Article
Language:English
Published: United States 03.07.2023
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Abstract Serum 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). Over 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. Twenty 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. These findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA. Octave Bioscience, Inc (Menlo Park, CA).
AbstractList Serum 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). Over 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. Twenty 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. These findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA. Octave Bioscience, Inc (Menlo Park, CA).
Serum 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).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).Over 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.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.Twenty 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.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.These findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA.DiscussionThese findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA.Octave Bioscience, Inc (Menlo Park, CA).FundingOctave Bioscience, Inc (Menlo Park, CA).
Author Caillier, Stacy J
Lokhande, Hrishikesh
Sattarnezhad, Neda
Chitnis, Tanuja
Weiner, Howard
Yano, Hajime
Bove, Riley
Hauser, Stephen L
Cree, Bruce A C
Katrib, Amal
Baranzini, Sergio E
Henry, Roland G
Gomez, Refujia
Saxena, Shrishti
Paul, Anu
Qureshi, Ferhan
Gehman, Victor M
Santaniello, Adam
Becich, Michael
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References 38769309 - Nat Commun. 2024 May 20;15(1):4297
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