Identification of Metabolite Biomarkers for Gout Using Capillary Ion Chromatography with Mass Spectrometry

Gout is a common form of inflammatory arthritis, and the detailed pathogenic mechanisms for this metabolic disorder remain largely unknown. In this study, we first profiled the salivary metabolites in 8 patients with gout, 15 patients with hyperuricaemia (HUA), and 15 healthy individuals using capillary ion chromatography (CIC) with tandem mass spectrometry (MS/MS). Forty-nine salivary metabolites were found to be significantly changed between gout patient and healthy control groups, and 26 salivary metabolites were significantly different between gout and HUA patient groups. Three metabolite biomarkers, uric acid, oxalic acid, and l-homocysteic acid (HCA), were selected for validation in the saliva samples of 30 patients with gout, 30 patients with HUA, and 30 healthy control subjects. By using commercial assay kits for the measurements, salivary uric acid and oxalic acid levels were found to be significantly higher in gout patients than healthy controls, whereas salivary HCA level was significantly higher in gout patients than both HUA patients and healthy controls. These assay measurements were in line with those obtained by CIC-MS/MS. In conclusion, we have demonstrated a new application of CIC-MS/MS for the discovery of novel metabolite biomarkers of gout. Validated biomarkers may be used for noninvasive, diagnostic and prognostic applications in gout. Future studies are warranted to investigate the clinical utility of these identified biomarkers for monitoring gout flare and/or treatment efficacy.