Metabolomics of inflammatory arthritis

Kapoor, Sabrina Reenu (2014). Metabolomics of inflammatory arthritis. University of Birmingham. Ph.D.

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Abstract

Background Rheumatoid arthritis (RA) is associated with both local and systemic inflammation which influences the function of the whole body as well as local tissues in the joints. Significant consequences of this are changes in metabolism. Hence, we hypothesised that chronic inflammation alters metabolism and that the metabolic profile of an individual patient with early inflammatory arthritis predicts the subsequent course of disease. Furthermore, we suggested that these metabolic changes would identify biomarkers of response to treatment in inflammatory arthritis and provide novel insights into disease mechanisms.

Methods Using NMR spectroscopy of serum, urine and synovial fibroblasts we derived metabolic profiles and subjected these to multi-parameter analyses to identify metabolic differences associated with inflammation.

Results We were able to predict outcome in patients with early arthritis using material derived from cultured synovial fibroblasts but were unable to do so using serum. There was a significant association between CRP levels in the patients’ serum and the metabolic profile of their synovial fibroblasts and their serum. There was also a significant association between the metabolomic fingerprint of synovial fibroblasts and the fibroblasts’ IL6 production. We found differences in metabolites between urine samples of RA and psoriatic arthritis (PsA) patients and were able to predict responses to anti-TNF therapy in patients with RA.

Discussion Our results demonstrate that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood, synovial fibroblasts and urine samples in patients with inflammatory arthritis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):