title: Metabolomics study of fatigue in patients with rheumatoid arthritis naïve to biological treatment.
abstract: Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions. Patients often regard fatigue as one of their most debilitating problems, but currently there is no established treatment and the mechanisms that lead to and regulate fatigue are incompletely understood. Our objective was to more completely understand the physiology of this phenomenon. Twenty-four patients with rheumatoid arthritis (RA) naïve to treatment with biological drugs were enrolled for the study. Fatigue was measured with a fatigue visual analogue scale (fVAS). Ethylenediaminetetraacetic acid (EDTA) plasma samples were subjected to gas chromatography-time-of-flight mass spectrometry (GC/MS-TOF)-based metabolite profiling. Obtained metabolite data were evaluated by multivariate data analysis with orthogonal projections to latent structures (OPLS) method to pinpoint metabolic changes related to fatigue severity. A significant multivariate OPLS model was obtained between the fVAS scores and the measured metabolic levels. Increasing fatigue scores were associated with a metabolic pattern characterized by down-regulation of metabolites from the urea cycle, fatty acids, tocopherols, aromatic amino acids, and hypoxanthine. Uric acid levels were increased. Apart from fatigue, we found no other disease-related variables that might be responsible for these changes. Our MS-based metabolomic approach demonstrated strong associations between fatigue and several biochemical patterns related to oxidative stress.
authors.affiliation: Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 901-87, Umeå, Sweden.
authors.forename: Izabella
authors.initials: I
authors.lastname: Surowiec
authors.affiliation: Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Clara Gram
authors.initials: CG
authors.lastname: Gjesdal
authors.affiliation: Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Grete
authors.initials: G
authors.lastname: Jonsson
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Katrine Brække
authors.initials: KB
authors.lastname: Norheim
authors.affiliation: Acureomics AB, Umeå, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundstedt
authors.affiliation: Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 901-87, Umeå, Sweden. johan.trygg@umu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Roald
authors.initials: R
authors.lastname: Omdal
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000378:metabolism*; D005221:Fatigue / Q000150:complications / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged
keywords: Fatigue; Metabolomics; Oxidative stress; Rheumatoid arthritis