TY - JOUR
T1 - Metabolomic signatures associated with disease severity in multiple sclerosis
AU - Villoslada, Pablo
AU - Alonso, Cristina
AU - Agirrezabal, Ion
AU - Kotelnikova, Ekaterina
AU - Zubizarreta, Irati
AU - Pulido-Valdeolivas, Irene
AU - Saiz, Albert
AU - Comabella, Manuel
AU - Montalban, Xavier
AU - Villar, Luisa
AU - Alvarez-Cermeño, Jose Carlos
AU - Fernández, Oscar
AU - Alvarez-Lafuente, Roberto
AU - Arroyo, Rafael
AU - Castro, Azucena
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017
Y1 - 2017
N2 - Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: A retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS >3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course.
AB - Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: A retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS >3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course.
UR - http://www.scopus.com/inward/record.url?scp=85019584324&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000321
DO - 10.1212/NXI.0000000000000321
M3 - Article
AN - SCOPUS:85019584324
SN - 2332-7812
VL - 4
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 2
M1 - e321
ER -