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Metabolomics study of fatigue in patients with rheumatoid arthritis naïve to biological treatment

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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.

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Acknowledgments

This study was funded by Swedish Research Council Grant No. 2011-6044. KN was funded by the Norwegian Western Health Authorities (Grant No: 911783). RO received an unrestricted grant from Pfizer of 100,000 NOK for research on fatigue in RA and in ankylosing spondylitis.

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    Authors and Affiliations

    1. Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, 901-87, Umeå, Sweden

      Izabella Surowiec & Johan Trygg

    2. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway

      Clara Gram Gjesdal

    3. Department of Clinical Science, University of Bergen, Bergen, Norway

      Clara Gram Gjesdal & Roald Omdal

    4. Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway

      Grete Jonsson

    5. Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway

      Katrine Brække Norheim & Roald Omdal

    6. Acureomics AB, Umeå, Sweden

      Torbjörn Lundstedt

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    1. Izabella Surowiec
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    Correspondence to Johan Trygg.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Johan Trygg and Roald Omdal have contributed equally to the work.

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    Surowiec, I., Gjesdal, C.G., Jonsson, G. et al. Metabolomics study of fatigue in patients with rheumatoid arthritis naïve to biological treatment. Rheumatol Int 36, 703–711 (2016). https://doi.org/10.1007/s00296-016-3426-2

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    • DOI: https://doi.org/10.1007/s00296-016-3426-2

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