Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis

Abstract Gray matter demyelinating lesions, brain atrophy and meningeal inflammation are hypothesized to be relevant in multiple sclerosis (MS) disease pathogenesis, though their relationship to immune alterations in early MS is not well characterized. This study aims to investigate correlations bet...

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Main Authors: Andrei Miclea, Jonathan Zurawski, Brian C. Healy, Shrishti Saxena, Hrishikesh Lokhande, Molly Quattrucci, Renxin Chu, Howard L. Weiner, Rohit Bakshi, Tanuja Chitnis
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95229-x
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author Andrei Miclea
Jonathan Zurawski
Brian C. Healy
Shrishti Saxena
Hrishikesh Lokhande
Molly Quattrucci
Renxin Chu
Howard L. Weiner
Rohit Bakshi
Tanuja Chitnis
author_facet Andrei Miclea
Jonathan Zurawski
Brian C. Healy
Shrishti Saxena
Hrishikesh Lokhande
Molly Quattrucci
Renxin Chu
Howard L. Weiner
Rohit Bakshi
Tanuja Chitnis
author_sort Andrei Miclea
collection DOAJ
description Abstract Gray matter demyelinating lesions, brain atrophy and meningeal inflammation are hypothesized to be relevant in multiple sclerosis (MS) disease pathogenesis, though their relationship to immune alterations in early MS is not well characterized. This study aims to investigate correlations between the concentrations of 112 serum proteins and 7 Tesla MRI-defined measures of disease severity in patients with early MS. In this analysis, patients with CIS or MS having a 7 Tesla brain MRI and blood sample both within five years of MS diagnosis were included (n = 57). Correlational analysis was adjusted for sex, age, and disease duration. Correlation between serum proteins and MRI-defined cortical and thalamic gray matter lesions, leptomeningeal enhancement (presence and foci number), deep gray matter (DGM) structure volumes, whole brain parenchymal volume and total T2 white matter lesion volume was assessed. In this study, cortical lesions were associated with higher IL-15, TNF-alpha, and BAFF levels, and lower levels of FcRL2. Leptomeningeal enhancement was associated with higher levels of PLXNB3 and lower levels of nCDase and CNTN5. Higher IL-1B levels correlated with lower DGM volume while higher levels of CDH6, SIGLEC9, and HAGH correlated with higher DGM volume. These novel associations between serum immune proteins and 7 T MRI outcomes may have relevance as disease biomarkers in early stages of MS.
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spelling doaj-art-d457db412f774b3280bb8466ff8a94d42025-08-20T02:17:05ZengNature PortfolioScientific Reports2045-23222025-04-0115111410.1038/s41598-025-95229-xNovel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosisAndrei Miclea0Jonathan Zurawski1Brian C. Healy2Shrishti Saxena3Hrishikesh Lokhande4Molly Quattrucci5Renxin Chu6Howard L. Weiner7Rohit Bakshi8Tanuja Chitnis9Brigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalBrigham Multiple Sclerosis Center, Brigham and Women’s HospitalAbstract Gray matter demyelinating lesions, brain atrophy and meningeal inflammation are hypothesized to be relevant in multiple sclerosis (MS) disease pathogenesis, though their relationship to immune alterations in early MS is not well characterized. This study aims to investigate correlations between the concentrations of 112 serum proteins and 7 Tesla MRI-defined measures of disease severity in patients with early MS. In this analysis, patients with CIS or MS having a 7 Tesla brain MRI and blood sample both within five years of MS diagnosis were included (n = 57). Correlational analysis was adjusted for sex, age, and disease duration. Correlation between serum proteins and MRI-defined cortical and thalamic gray matter lesions, leptomeningeal enhancement (presence and foci number), deep gray matter (DGM) structure volumes, whole brain parenchymal volume and total T2 white matter lesion volume was assessed. In this study, cortical lesions were associated with higher IL-15, TNF-alpha, and BAFF levels, and lower levels of FcRL2. Leptomeningeal enhancement was associated with higher levels of PLXNB3 and lower levels of nCDase and CNTN5. Higher IL-1B levels correlated with lower DGM volume while higher levels of CDH6, SIGLEC9, and HAGH correlated with higher DGM volume. These novel associations between serum immune proteins and 7 T MRI outcomes may have relevance as disease biomarkers in early stages of MS.https://doi.org/10.1038/s41598-025-95229-xBiomarkers7 TeslaLeptomeningeal enhancementCortical lesionsDeep gray matter lesionsMultiple sclerosis
spellingShingle Andrei Miclea
Jonathan Zurawski
Brian C. Healy
Shrishti Saxena
Hrishikesh Lokhande
Molly Quattrucci
Renxin Chu
Howard L. Weiner
Rohit Bakshi
Tanuja Chitnis
Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
Scientific Reports
Biomarkers
7 Tesla
Leptomeningeal enhancement
Cortical lesions
Deep gray matter lesions
Multiple sclerosis
title Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
title_full Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
title_fullStr Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
title_full_unstemmed Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
title_short Novel serum biomarker associations with 7 Tesla MRI-defined cortical lesions, leptomeningeal enhancement, and deep gray matter volume in early multiple sclerosis
title_sort novel serum biomarker associations with 7 tesla mri defined cortical lesions leptomeningeal enhancement and deep gray matter volume in early multiple sclerosis
topic Biomarkers
7 Tesla
Leptomeningeal enhancement
Cortical lesions
Deep gray matter lesions
Multiple sclerosis
url https://doi.org/10.1038/s41598-025-95229-x
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