The Impact of Inflammation on Metabolomic Profiles in Patients With Arthritis

Authors

  • Stephen P. Young,

    Corresponding author
    1. University of Birmingham, Birmingham, UK
    • Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, UK. E-mail: s.p.young@bham.ac.uk

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    • Drs. Young and Kapoor contributed equally to this work.

  • Sabrina R. Kapoor,

    1. University of Birmingham and the Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
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    • Drs. Young and Kapoor contributed equally to this work.

  • Mark R. Viant,

    1. University of Birmingham, Birmingham, UK
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  • Jonathan J. Byrne,

    1. University of Birmingham, Birmingham, UK
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  • Andrew Filer,

    1. University of Birmingham and the University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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  • Christopher D. Buckley,

    1. University of Birmingham and the Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
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  • George D. Kitas,

    1. University of Birmingham and the Dudley Group of Hospitals NHS Foundation Trust, Birmingham, UK
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    • Dr. Kitas has received consulting fees from AstraZeneca (less than $10,000) and speaking fees and/or honoraria for Advisory Board service from Roche, Abbott, Pfizer, Novartis, UCB, and Bristol-Myers Squibb (less than $10,000 each) and has received unrestricted grants from Pfizer.

  • Karim Raza

    1. University of Birmingham and the Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
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Abstract

Objective

Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess metabolic fingerprints in serum from patients with established rheumatoid arthritis (RA) and those with early arthritis.

Methods

Serum samples were collected from newly presenting patients with established RA who were naive for disease-modifying antirheumatic drugs, matched healthy controls, and 2 groups of patients with synovitis of ≤3 months' duration whose outcomes were determined at clinical followup. Serum metabolomic profiles were assessed using 1-dimensional 1H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolomic profiles and clinical variables including outcomes were examined.

Results

The serum metabolic fingerprint in established RA was clearly distinct from that of healthy controls. In early arthritis, we were able to stratify the patients according to the level of current inflammation, with C-reactive protein correlating with metabolic differences in 2 separate groups (P < 0.001). Lactate and lipids were important discriminators of inflammatory burden in both early arthritis patient groups. The sensitivities and specificities of models to predict the development of either RA or persistent arthritis in patients with early arthritis were low.

Conclusion

The metabolic fingerprint reflects inflammatory disease activity in patients with synovitis, demonstrating that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood. The identification of metabolic alterations may provide insights into disease mechanisms operating in patients with inflammatory arthritis.

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