Serum Metabolic Signatures of Four Types of Human Arthritis

Abstract

Similar symptoms of the different types of arthritis have continued to confound the clinical diagnosis and represent a clinical dilemma making treatment choices with a more personalized or generalized approach. Here we report a mass spectrometry-based metabolic phenotyping study to identify the global metabolic defects associated with arthritis as well as metabolic signatures of four major types of arthritis--rheumatoid arthritis (n = 27), osteoarthritis (n = 27), ankylosing spondylitis (n = 27), and gout (n = 33)--compared with healthy control subjects (n = 60). A total of 196 metabolites were identified from serum samples using a combined gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF MS) and ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-QTOF MS). A global metabolic profile is identified from all arthritic patients, suggesting that there are common metabolic defects resulting from joint inflammation and lesion. Meanwhile, differentially expressed serum metabolites are identified constituting an unique metabolic signature of each type of arthritis that can be used as biomarkers for diagnosis and patient stratification. The results highlight the applicability of metabonomic phenotyping as a novel diagnostic tool for arthritis complementary to existing clinical modalities.

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

“…In a similar approach using plasma samples, patients with knee OA were found to have lower levels of arginine 20 . Finally, a metabolomics study that examined serum samples from healthy controls and patients with osteoarthritis, rheumatoid arthritis (RA), ankylosing spondylitis and gout, found that the patients with arthritis could be differentiated from the controls and that each form of arthritis had a distinct metabolite profile 42 .…”

Metabolomics in rheumatic diseases: desperately seeking biomarkers

“…Notably, glucose deprivation or treatment with glycolytic inhibitors such as 2-deoxy-D-glucose and bromopyruvate impaired cytokine secretion, proliferation and migration in FLSs, and glycolytic inhibition by bromopyruvate administered in vivo in a serum-transfer animal model significantly decreased arthritis severity compared with untreated animals 118 . Thus, the increase in lactate detected in metabolomics studies 95,96 could be secondary to the increase in glycolysis in FLSs.…”

“…In a comparison of serum metabolic signatures in OA, RA, ankylosing spondylitis and gout by MS 95 , homoserine, 4,8-dimethylnonanoyl carnitine, glyceraldehyde, lactic acid, dihydroxyfumaric acid and aspartic acid were identified as candidate markers in the four types of arthritis, compared with healthy controls. In another study, with 1 H-NMR characterization of serum samples from patients with established RA, early arthritis and healthy controls, levels of several metabolites, such as 3-hydroxybutyrate, glucose, lactate, and urea, were correlated with the extent of inflammation 96 .…”

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

“…profiled the metabolomic differences of four types of arthritis using GC-MS and LC-MS with 198 annotated features included in statistical analysis. They found elevated energy metabolism and pyruvate to lactate pathway in these samples22. However, none of these studies was focused on using metabolomics to monitor OA progression and treatment.…”

“…Several metabolomic profiling studies using human subjects and animal models have been reported on the investigation of metabolic responses to OA using biofluids such as urine, plasma and synovial fluids1819202122. Li et al .…”