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.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1655-3) contains supplementary material, which is available to authorized users.

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Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that has transitioned from a debilitating disease to a chronic, controllable disease. This has been possible due to the introduction of new treatment strategies like "treat-to-target," in which the clinician treats the patient aggressively enough to reach low disease activity or remission, and the introduction of new therapeutic agents, such as biological therapies, which can lead to the prevention of damage by early diagnosis and initiation of treatment. Attention is now being directed toward identifying the optimal treatment for each patient, one that will be the most efficient and have the least number of side effects. Much work has been done to find serologic and synovial biomarkers of response to various RA treatments. Proteomics, genomics and, in the past few years, metabolomics, have all been used in the quest of identifying these biomarkers. Blood-based liquid biopsies provide a minimally invasive alternative to synovial biopsies to identify cellular and molecular signatures that can be used to longitudinally monitor response and allow for personalized medicine approach. Liquid biopsies are comprised of cell-free DNA, immune circulating cells, and extracellular vesicles, and are being increasingly and successfully used in the field of oncology for diagnosis, progression, prognosis, and prediction of response to treatment. Recently, researchers have also begun investigating the usefulness of liquid biopsies in the field of rheumatology; in this review, we will focus on the potential of liquid biopsy blood samples as biomarkers of response to treatment in patients with RA.

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