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Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis.

Gurpreet Singh Jutley1, Kalvin Sahota1, Ilfita Sahbudin1

  • 1NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.

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|October 15, 2021
PubMed
Summary

Systemic inflammation in rheumatoid arthritis (RA) is linked to metabolic changes. This study reveals a connection between C-reactive protein (CRP) levels and both serum and urine metabolic profiles in early RA patients.

Keywords:
cachexiacitrate cycleglycolysisinflammationmetabolismoxidative stressrheumatoid arthritisurea cycle

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Area of Science:

  • Biochemistry
  • Immunology
  • Metabolomics

Background:

  • Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic alterations.
  • Understanding these metabolic changes is crucial for RA pathogenesis.

Purpose of the Study:

  • To investigate the relationship between C-reactive protein (CRP), an objective measure of inflammation, and the serum and urinary metabolome in newly presenting RA patients.
  • To identify metabolic perturbations associated with elevated inflammation in early RA.

Main Methods:

  • Utilized 1-dimensional proton nuclear magnetic resonance (1H-NMR) spectroscopy for metabolomic profiling of serum (n=126) and urine (n=83) samples from RA patients.
  • Employed partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) for data analysis.

Main Results:

  • A significant correlation was found between CRP levels and both serum (p=0.001) and urinary (p<0.001) metabolomes.
  • OPLS-DA successfully discriminated between patients in the lowest and highest CRP tertiles using both serum (p=0.033) and urinary (p<0.001) metabolomic data.
  • Key metabolites implicated included glucose, amino acids, lactate, and citrate, suggesting increased glycolysis, altered citrate cycle, oxidative stress, and protein/urea cycle activity.

Conclusions:

  • Confirms the link between serum metabolite profiles and inflammation in RA.
  • Provides novel evidence for a relationship between urinary metabolite profiles and inflammation (CRP) in RA.
  • Identified metabolic perturbations offer insights into RA pathogenesis and potential therapeutic targets.