Abstract
BackgroundMetabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Here, we explore the hypothesis of whether characterization of patients’ metabolomic profiles in blood, utilizing 1H-nuclear magnetic resonance (NMR), predicts synovial marker profiling in rheumatoid arthritis (RA).MethodsNineteen active, seropositive patients with RA, on concomitant methotrexate, were studied. One of the involved joints was a knee or a wrist appropriate for arthroscopy. A Bruker Avance 700 MHz spectrometer was used to acquire NMR spectra of serum samples. Gene expression in synovial tissue obtained by arthroscopy was analyzed by real-time PCR. Data processing and statistical analysis were performed in Python and SPSS.ResultsAnalysis of the relationships between each synovial marker-metabolite pair using linear regression and controlling for age and gender revealed significant clustering within the data. We observed an association of serine/glycine/phenylalanine metabolism and aminoacyl-tRNA biosynthesis with lymphoid cell gene signature. Alanine/aspartate/glutamate metabolism and choline-derived metabolites correlated with TNF-α synovial expression. Circulating ketone bodies were associated with gene expression of synovial metalloproteinases. Discriminant analysis identified serum metabolites that classified patients according to their synovial marker levels.ConclusionThe relationship between serum metabolite profiles and synovial biomarker profiling suggests that NMR may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium of patients with RA.
Highlights
Metabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis
As shown in Additional file 1: Table S3 and Fig. 2a, most of the metabolites were downregulated compared to reference values, suggesting that these metabolites might be consumed by the inflamed synovium due to an increase in its metabolic demand
Studies in other cohorts of patients with active rheumatoid arthritis (RA) are needed to validate these results, yet the relationship between serum metabolic profiles and synovial biomarker profiling suggests that nuclear magnetic resonance (NMR) may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium in RA
Summary
Metabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Narasimhan et al Arthritis Research & Therapy (2018) 20:164 understanding of the pathogenic events in these diseases [5]. Histopathotype and pathological pathways-based patient stratification prior to therapeutic intervention could be exploited to identify biomarker predictors of clinical outcomes and responses to therapy [6, 7]. Metabolomics is an emerging field of biomedical research that can offer a better understanding of the mechanisms underlying disease and help to develop new strategies for treatment [11]. Unlike genes and proteins, which are epigenetically regulated and post-translationally modified, metabolites are direct signatures of biochemical activity and it may be easier to test whether they are correlated with phenotype [12]
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