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Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation
Dejan Jakimovski1, Ferhan Qureshi2, Murali Ramanathan3
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Background:
Atrophied lesion volume (aLV), a proposed biomarker of disability progression in multiple sclerosis (MS) and transition into progressive MS (PMS), depicts chronic periventricular white matter (WM) pathology. Meningeal infiltrates, imaged as leptomeningeal contrast enhancement (LMCE), are linked with greater cortical pathology.
Objectives:
To determine the relationship between serum-derived proteomic data with the development of aLV and LMCE in a heterogeneous group of people with MS (pwMS).
Methods:
Proteomic and MRI data for 202 pwMS (148 clinically isolated syndrome /relapsing-remitting MS and 54 progressive MS (PMS)) were acquired at baseline and at 5.4-year follow-up. The concentrations of 21 proteins related to multiple MS pathophysiology pathways were derived using a custom-developed Proximity Extension Assay on the Olink™ platform. The accrual of aLV was determined as the volume of baseline T2-weighted lesions that were replaced by cerebrospinal fluid over the follow-up. Regression models and age-adjusted analysis of covariance (ANCOVA) were used.
Results:
Older age (standardized beta = 0.176, p = 0.022), higher glial fibrillary acidic protein (standardized beta = 0.312, p = 0.001), and lower myelin oligodendrocyte glycoprotein levels (standardized beta = -0.271, p = 0.002) were associated with accrual of aLV over follow-up. This relationship was driven by the pwPMS population. The presence of LMCE at the follow-up visit was not predicted by any baseline proteomic biomarker nor cross-sectionally associated with any protein concentration.
Conclusion:
Proteomic markers of glial activation are associated with chronic lesional WM pathology (measured as aLV) and may be specific to the progressive MS phenotype. LMCE presence in MS does not appear to relate to proteomic measures.
Insights
Glial activation markers in the blood are linked to white matter lesion atrophy in progressive multiple sclerosis (MS). These proteomic markers do not predict leptomeningeal contrast enhancement in MS patients.
Area of Science:
- Neurology
- Biomarker Discovery
- Proteomics
Background:
- Atrophied lesion volume (aLV) indicates chronic white matter pathology and disability progression in multiple sclerosis (MS).
- Leptomeningeal contrast enhancement (LMCE) is associated with greater cortical pathology in MS.
Purpose of the Study:
- To investigate the association between serum proteomic data and the development of aLV and LMCE in people with MS (pwMS).
Main Methods:
- Proteomic analysis of 21 MS-related proteins using Olink™ platform on samples from 202 pwMS.
- MRI data (aLV, LMCE) acquired at baseline and 5.4-year follow-up.
- Statistical analysis using regression models and ANCOVA.
Main Results:
- Higher glial fibrillary acidic protein and lower myelin oligodendrocyte glycoprotein levels were associated with aLV accrual, particularly in the progressive MS (PMS) population.
- Older age also correlated with aLV accrual.
- No baseline proteomic biomarker predicted LMCE at follow-up or showed cross-sectional association.
Conclusions:
- Proteomic markers of glial activation are linked to chronic white matter pathology (aLV) in MS, potentially specific to the progressive phenotype.
- Leptomeningeal contrast enhancement in MS is not associated with the studied proteomic measures.
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