The treatment-naive Rheumatoid Arthritis metabolome

Aims: Alterations in metabolic pathways that drive inflammation have been observed in patients with rheumatoid arthritis (RA). However,whether the peripheral metabolic profiles of patients with RA can be used as biomarkers of diagnosis, prognosis, therapy response and degree of ongoing disease activity remain lacking. To address this, we sought to examine and profile biochemical variations in the serum of patients with early, treatment-naïve RA and matched healthy controls.

Methods: Serum samples from patients with treatment-naïve, early RA(n = 50) and a matched cohort of healthy controls (n = 30) were prepared for analysis using Metabolon® Platform Technology (NC, USA) and global metabolomic profiles generated. Statistical analyses were performed using ArrayStudio, R (http://cran.r-project.org/) and JMP. P-values < 0.0 5were deemed statistically significant.

Results: Our analysis identified a total of 933 biochemicals. Global biochemical profiles differed drastically between RA patients and healthy controls, revealing a number of potentially strong RA serum biomarkers. A major difference was associated with the benzoate metabolic pathway, indicating a possible fungal origin. Additionally, several altered biochemical pathways in the RA serum from this study have previously been indicated to be altered in RA, including sphingolipids, serotonin, taurine, fibrinogen peptides and altered steroid hormone levels. We also observed an apparent increase in glycolytic and TCA cycle activity was in the RA serum,suggesting increased energetic activity.

Conclusions: Here we identify altered metabolic pathways in RA with inter-mediates that may potentially serve as serum soluble RA biomarkers, and 11 of these were indicated as potentially very strong candidates (by p-value and Random Forest Analysis). The data presented here suggest that several biochemical pathways are altered in RA, including benzoate, serotonin, taurine, and sphingolipid metabolism, and that further investigation into these pathways may enable the discovery of informative peripheral biomarkers for RA.