National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China; State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Nanchang, 330006, China.
Semin Arthritis Rheum. 2022 Aug;55:152022. doi: 10.1016/j.semarthrit.2022.152022. Epub 2022 May 5.
The gouty arthritis (GA) progression was multistage, yet the GA clinical diagnosis guidelines were more inclined to suitable for acute gouty arthritis (AGA), thus neglecting of the progress of GA. This study aimed to identify specific biomarkers that were competent for reflecting the progression of GA and attempted to provide evidence for seasonable intervention of appropriate clinical treatment.
A total of 547 patients with GA at sequential stages and healthy volunteers were divided into a training set (n = 347) and a validation set (n = 200). Serum metabolic profiles were determined by UHPLC-QTOF-MS-MS untargeted metabolomics, and biomarkers were identified by logistic regression and receiver operating characteristic analysis. Further, UHPLC-QE-MS was applied for accurate quantitative validation of identified potential biomarkers in the validation set samples.
After serum metabolic profiles analysis by untargeted metabolomics, 12 metabolites with monotonous change trend were screened, and were verified by targeted metabolomics subsequently. The quantitative results showed the serum concentration of kynurenic acid(KYNA), N1-Methyl-2-pyridone-5-carboxamide(2PY), DL-2-Aminoadipic acid(2AMIA) and 5-hydroxyindole acetic acid(5-HIAA) of patients with sequential stages showed a strictly monotonic trend, and AUC was 0.97, 0.97, 0.96 and 0.95, respectively.
KYNA and 5-HIAA are related to acute inflammation of GA, while 2PY and 2AMIA are related to renal function damage caused by long-term HUA. Therefore, we believe it is inappropriate to use a single biomarker to define the phase of GA. Actually, four biomarkers obtained in this paper should be integratedly adopted to evaluate the progression of GA with sequential stages.
痛风性关节炎（GA）的进展是多阶段的，但 GA 的临床诊断指南更倾向于适合急性痛风性关节炎（AGA），因此忽略了 GA 的进展。本研究旨在寻找能够反映 GA 进展的特定生物标志物，并尝试为及时干预合适的临床治疗提供证据。
将 547 例连续阶段 GA 患者和健康志愿者分为训练集（n=347）和验证集（n=200）。采用 UHPLC-QTOF-MS-MS 非靶向代谢组学方法测定血清代谢谱，采用逻辑回归和受试者工作特征分析筛选生物标志物。进一步应用 UHPLC-QE-MS 对验证集样本中鉴定的潜在生物标志物进行准确的定量验证。
通过非靶向代谢组学分析血清代谢谱后，筛选出 12 种具有单调变化趋势的代谢物，随后通过靶向代谢组学进行验证。定量结果显示，连续阶段患者血清中犬尿氨酸（KYNA）、N1-甲基-2-吡啶酮-5-甲酰胺（2PY）、DL-2-氨基己二酸（2AMIA）和 5-羟吲哚乙酸（5-HIAA）的浓度呈严格单调趋势，AUC 分别为 0.97、0.97、0.96 和 0.95。
KYNA 和 5-HIAA 与 GA 的急性炎症有关，而 2PY 和 2AMIA 与长期 HUA 引起的肾功能损害有关。因此，我们认为使用单一生物标志物来定义 GA 的阶段是不合适的。实际上，本文获得的四个生物标志物应该综合采用，以评估具有连续阶段的 GA 的进展。
