Background/Purpose: Rheumatoid arthritis (RA) is a chronic, inflammatory disease characterized by persistent inflammation and joint damage with a heterogeneous course and different pathogenic mechanisms. Metabolomics, defined as the comprehensive analysis of the small-molecule metabolites in a biological system, is a rapidly developing biomedical research area. This study was to investigate metabolic perturbation in the synovial fluid (SF) of RA patients according to the degree of disease activity using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) to gain more insight into the pathologic metabolic alterations in RA.

Methods: We included 47 patients with diagnosed active RA (15 male, 32 female). Disease activity was assessed using DAS28-ESR. SF metabolomic profiling was performed was performed using GC/TOF MS, in conjunction with multivariate statistical analyses and pathway analyses such as metabolite set enrichment analysis (MSEA).

Results: A total of 125 metabolites were identified from SF of RA, which were classified into various chemical classes, such as amino acids (21% of identified metabolites), organic acids (21%), sugar and sugar alcohols (18%), fatty acids (14%), amines (9%), and phosphates (5%).

We indicated statistical significant correlation between DAS28-ESR value and the intensities of 12 metabolites (β-alanine, asparagine, citrate, cyano-L-alanine, indol-3-lactate, leucine, nicotinamide, citrulline, methionine, oxoproline, salicylaldehyde, and glycocyamine). The intensities of glycocyamine and indol-3-lactate positively correlated with DAS28-ESR value (rho = 0.311, p = 0.017; rho = 0.345, p = 0.033). On the other hand, β-alanine, asparagine, citrate, cyano-L-alanine, leucine, nicotinamide, citrulline, methionine, oxoproline, and salicylaldehyde negatively correlated with DAS28-ESR.

To investigate whether metabolism is affected by disease activity in RA, we have performed MSEA and metabolic pathway analysis by using MetaboAnalyst. We found that the higher the disease activity, the more amino acid metabolic processes were affected. In MSEA, we found six unique pathways, namely, fructose and mannose degradation, phenylalanine and tyrosine metabolism, citric acid cycle, galactose metabolism, tryptophan metabolism and pyrimidine metabolism that were significantly associated with disease activity in RA.

Conclusion: Synovial metabolite perturbations, especially perturbation in amino acid metabolism, are suggested to be correlated with disease activity of RA. SF metabolomic approaches based on GC/TOF-MS can provide important information relating to monitor disease activity in RA and be important approach to understanding the altered metabolism and pathophysiology of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/variation-in-the-synovial-fluid-metabolome-according-to-disease-activity-in-rheumatoid-arthritis/