School of Dentistry, University of California , Los Angeles, California 90095, United States.
Changzhou Second People's Hospital, Nanjing Medical University , Changzhou 213000, China.
Anal Chem. 2017 Nov 7;89(21):11737-11743. doi: 10.1021/acs.analchem.7b03232. Epub 2017 Oct 19.
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.
痛风是一种常见的炎性关节炎，其代谢紊乱的详细发病机制仍很大程度上未知。在这项研究中，我们首先使用毛细管离子色谱（CIC）与串联质谱（MS/MS）对 8 例痛风患者、15 例高尿酸血症（HUA）患者和 15 例健康个体的唾液代谢物进行了分析。在痛风患者和健康对照组之间发现了 49 种唾液代谢物存在显著差异，在痛风和 HUA 患者组之间发现了 26 种唾液代谢物存在显著差异。选择尿酸、草酸和 l-高半胱氨酸（HCA）这三种代谢物生物标志物，在 30 例痛风患者、30 例 HUA 患者和 30 例健康对照组的唾液样本中进行验证。通过使用商业试剂盒进行测量，发现痛风患者的唾液尿酸和草酸水平明显高于健康对照组，而痛风患者的唾液 HCA 水平明显高于 HUA 患者和健康对照组。这些测定结果与 CIC-MS/MS 一致。总之，我们展示了 CIC-MS/MS 在发现痛风新型代谢物生物标志物方面的新应用。验证后的生物标志物可用于痛风的非侵入性诊断和预后应用。未来的研究需要进一步探讨这些鉴定出的生物标志物在监测痛风发作和/或治疗效果方面的临床应用价值。
