Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation

Dejan Jakimovski; Ferhan Qureshi; Murali Ramanathan; Kian Jalaleddini; Ati Ghoreyshi; Michael G Dwyer; Niels Bergsland; Bianca Weinstock-Guttman; Robert Zivadinov

doi:10.1016/j.jns.2024.123055

Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation

J Neurol Sci. 2024 May 14:461:123055. doi: 10.1016/j.jns.2024.123055. Online ahead of print.

Authors

Dejan Jakimovski¹, Ferhan Qureshi², Murali Ramanathan³, Kian Jalaleddini², Ati Ghoreyshi², Michael G Dwyer⁴, Niels Bergsland⁴, Bianca Weinstock-Guttman⁵, Robert Zivadinov⁶

Affiliations

¹ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: dejanjak@buffalo.edu.
² Octave Bioscience, Menlo Park, CA, USA.
³ Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
⁴ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
⁵ Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
⁶ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA.

PMID: 38761669
DOI: 10.1016/j.jns.2024.123055

Abstract

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.

Keywords: Atrophied lesion volume; Axonal injury; Glial fibrillary acidic protein; Leptomeningeal contrast enhancement; Multiple sclerosis; Proteomics.