University of Oxford
Department of Chemistry

Author Of 1 Presentation

Metabolomics Poster Presentation

P0530 - Understanding the metabolic profile of relapses in multiple sclerosis (ID 326)

Speakers
Presentation Number
P0530
Presentation Topic
Metabolomics

Abstract

Background

Accurate determination of relapses in multiple sclerosis (MS) is important for subtype classification and therapeutic decisions. However, there are currently no validated bio-fluid markers of relapses.

Objectives

To determine if metabolic perturbations are present during relapses, and if so, to identify candidate metabolite biomarkers and evaluate their discriminatory value both at group and individual levels, in comparison with serum neurofilament-light (NfL).

Methods

Global and targeted serum high resolution 1H nuclear magnetic resonance metabolomics and serum NfL (Simoa® assay) were performed on 4 groups of relapsing-remitting MS (RRMS) patients; (1) in relapses (in-R), (2) last relapse (LR) ≥1 month (M) to <6 M ago, (3) LR ≥6 M to <24 M ago, and (4) LR ≥24 M ago. Supervised multivariate analyses were used to determine metabolic differences between patient groups.

Results

Two hundred and one RRMS patients were recruited; in-R (n=38), LR 1–6 M (n=28), LR 6–24 M (n=34), LR ≥24 M (n=101). The global metabolic profile of in-R was significantly perturbed compared to LR ≥24 M (mean predictive accuracy ± SD, 62.6 ± 4.8% vs. 50.9 ± 8.2%; p <0.0001). Identified discriminatory metabolites were quantified, when possible, using targeted metabolomics. Lysine (high in-R), asparagine (high), isoleucine (low) and leucine (low) were shortlisted as potential metabolite biomarkers. One-way ANOVA of these metabolites showed significant differences across the 4 patient groups, with a clear trend (increasing or decreasing) with time away from relapse. Multivariable receiver operating characteristics (ROC) analysis of these 4 metabolites in discriminating in-R vs. LR ≥24 months showed an area under the curve (AUC) of 0.758, while serum NfL had an AUC of 0.575. Within individual patients (n=9) with paired relapse-remission samples (remission sample taken within 6 months of relapse), all 4 metabolites were significantly different in relapse and in remission, with directions consistent with that observed at group level, while serum NfL was not significant. Multivariable ROC of the 4 metabolites showed an AUC of 0.911. At group level, lysine and asparagine were higher in patients with gadolinium enhancing lesions in the last 1 year prior to sampling. No potential confounders were identified on further analyses, notably; none of in-R was on steroids at blood sampling.

Conclusions

Metabolomics identify perturbations in metabolites relating to energy deficiency and immune activation in relapses, and the use of these metabolites, singly or in combination, are useful in identifying relapses, both at group and individual level.

Collapse