Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis

Abstract

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

Nuclear magnetic resonance‐based metabolomics reveals similar metabolomics profiles in undifferentiated peripheral spondyloarthritis and reactive arthritis

“…Previous studies of metabolomics are present for RA and ankylosing spondylitis (AS) . Table summarizes the major metabolite disturbances reported in these studies as compared to our findings.…”

A discovery of screening markers for rheumatoid arthritis by liquid chromatography mass spectrometry: A metabolomic approach

“…28,29 Steroid deficiency in RA patients has already been identified in several studies. [30][31][32] Other studies have shown a deficiency of both steroids, as well as other kinds of steroids, suggesting that RA is associated with the steroid pathway. 32,33 These steroids are known to be present in lower concentrations in patients who did not receive corticosteroid treatment compared to those who received treatment.…”

“…[30][31][32] Other studies have shown a deficiency of both steroids, as well as other kinds of steroids, suggesting that RA is associated with the steroid pathway. 32,33 These steroids are known to be present in lower concentrations in patients who did not receive corticosteroid treatment compared to those who received treatment. 32 We confirmed that the patient group recruited for our study did not receive corticosteroid treatment.…”

“…32,33 These steroids are known to be present in lower concentrations in patients who did not receive corticosteroid treatment compared to those who received treatment. 32 We confirmed that the patient group recruited for our study did not receive corticosteroid treatment. The results of pathway analysis using final candidates in our study identified that the steroid hormone biosynthesis pathway is associated with RA, as reported in other studies ( Figure S4).…”

Variability of Two Metabolomic Platforms in CKD

“…Here, we utilize two leading metabolomics platforms operated by Metabolon (M) and the Broad Institute (B), both with established track records of investigation in human biomarker research (14)(15)(16)(17)(18)(19). We hypothesized that analyses of a common set of samples obtained from patients with CKD on both nontargeted platforms would permit characterization of intraassay, day-to-day, and interassay variation as well as characterize the relationship between GFR and the metabolome.…”