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

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 inflam...

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Veröffentlicht in:	Nature communications Jg. 15; H. 1; S. 4297 - 12
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 20.05.2024 Nature Publishing Group Nature Portfolio
Schlagworte:	49 631/378/1689/1666 692/53/2421 692/617/375/1666 82/80 Adult Autoimmune diseases Biomarkers Biomarkers - blood Blood Proteins - analysis Cohort Studies Female Gadolinium Humanities and Social Sciences Humans Inflammation Inflammation - blood Magnetic Resonance Imaging - methods Male Middle Aged Modelling multidisciplinary Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - diagnostic imaging Network analysis Neurofilament Proteins - blood Proteins Proteomics Proteomics - methods Science Science (multidisciplinary) Serum proteins
ISSN:	2041-1723, 2041-1723
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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. Inflammatory and degenerative processes are thought to play a role in the pathophysiology of multiple sclerosis. Here, the authors identified twenty serum proteins associated with increased clinical and radiographic disease activity.
AbstractList	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.Inflammatory and degenerative processes are thought to play a role in the pathophysiology of multiple sclerosis. Here, the authors identified twenty serum proteins associated with increased clinical and radiographic disease activity. 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. 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. Inflammatory and degenerative processes are thought to play a role in the pathophysiology of multiple sclerosis. Here, the authors identified twenty serum proteins associated with increased clinical and radiographic disease activity. 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.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. 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.
ArticleNumber	4297
Author	Gehman, Victor M. Hauser, Stephen L. Lokhande, Hrishikesh Sattarnezhad, Neda Chitnis, Tanuja Weiner, Howard Yano, Hajime Bove, Riley Henry, Roland G. Katrib, Amal Caillier, Stacy J. Cree, Bruce A. C. Gomez, Refujia Saxena, Shrishti Paul, Anu Qureshi, Ferhan Santaniello, Adam Baranzini, Sergio E. Becich, Michael
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SubjectTerms	49 631/378/1689/1666 692/53/2421 692/617/375/1666 82/80 Adult Autoimmune diseases Biomarkers Biomarkers - blood Blood Proteins - analysis Cohort Studies Female Gadolinium Humanities and Social Sciences Humans Inflammation Inflammation - blood Magnetic Resonance Imaging - methods Male Middle Aged Modelling multidisciplinary Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - diagnostic imaging Network analysis Neurofilament Proteins - blood Proteins Proteomics Proteomics - methods Science Science (multidisciplinary) Serum proteins
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Title	Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis
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