Several serum lipid metabolites are associated with relapse risk in pediatric-onset multiple sclerosis

Authors: VIRUPAKSHAIAH, AKASH - University Of California San Francisco (UCSF); LADAKIS, DIMITRIOS - Johns Hopkins University; NOURBAKHSH, BARDI - Johns Hopkins University; BHARGAVA, PAVAN - Johns Hopkins University; DILWALI, SONAM - University Of California San Francisco (UCSF); SCHOEPS, VINICIUS - University Of California San Francisco (UCSF); BORKOWSKI, KAMIL - University Of California, Davis; Newman, John; WAUBANT, EMMANUELLE - University Of California San Francisco (UCSF)

Submitted to: Multiple Sclerosis Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/2023
Publication Date: 5/18/2023
Citation: Virupakshaiah, A., Ladakis, D., Nourbakhsh, B., Bhargava, P., Dilwali, S., Schoeps, V., Borkowski, K., Newman, J.W., Waubant, E. 2023. Several serum lipid metabolites are associated with relapse risk in pediatric-onset multiple sclerosis. Multiple Sclerosis Journal. 29(8):936-944. https://doi.org/10.1177/13524585231171517.
DOI: https://doi.org/10.1177/13524585231171517

Interpretive Summary: The goal of this study was to determine if changes in patterns of lipid metabolites in the blood serum are associated with the risk of relapse and disability in children with multiple sclerosis (MS). To this end, we collected fasted serum samples from participants with pediatric-onset MS within four years of disease onset. We then prospectively collected data on MS relapse and level of disability using the Expanded Disability Status Scale (EDSS), a 10 pt standardized measure of disability ranging from fully functional to death. A comprehensive analysis of small molecules in the serum (i.e. untargeted metabolomics) was then performed, with the current study focusing on the lipid components. Individual metabolites were clustered into pre-defined pathways. The associations between sets of metabolites and either relapse rate or EDSS scores were estimated. In the study cohort consisted of 62 children with MS, we found that elevated serum acylcarnitines were associated with higher relapse rates and EDSS, while phosphatidylethanolamines, plasmalogens, and primary bile acid metabolites were associated with lower relapse rates and lower EDSS (q <0.05). This study suggests that alterations in specific lipid metabolic pathways are associated with disease course and severity in pediatric MS.

Technical Abstract: Objective: To determine if altered serum lipid metabolites are associated with the risk of relapse and disability in children with multiple sclerosis (MS). Methods: We collected fasted serum samples from participants with pediatric-onset MS within four years of disease onset. Prospective relapse data and disability (as measured by EDSS) were collected. Untargeted metabolomics was performed on plasma samples, but the current study focused on lipid metabolites. Individual metabolites were clustered into pre-defined pathways. The associations between sets of metabolites and relapse rate and Expanded Disability Status Scale (EDSS) score were estimated utilizing negative binomial and linear regression models, respectively. Results: Our cohort consisted of 62 children with MS. We found that acylcarnitines were associated with higher relapse rates and EDSS, while phosphatidylethanolamines, plasmalogens, and primary bile acid metabolites were associated with lower relapse rates and lower EDSS (q <0.05). Conclusions: This study suggests that alterations in specific lipid metabolic pathways area associated with disease course and severity in pediatric MS.