The impact of inflammation on metabolomic profiles in patients with arthritis

Objectives: Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We have used NMR spectroscopy-based metabolomics to assess metabolite fingerprints in serum from patients with established rheumatoid arthritis (RA) and early arthritis.
Methods: Serum samples were collected from newly presenting, disease-modifying drug naive patients with established RA, matched healthy controls, and two groups of patients with synovitis of 3 months’ duration whose outcomes were determined at clinical follow-up. Serum metabolic profiles were assessed using 1D 1H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolic profiles and clinical variables including outcomes were examined.
Results: The serum metabolite 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 CRP correlating with metabolic differences in two 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.
Conclusions: The metabolomic 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.