Abnormal kynurenine-pathway metabolites in gout: Biomarkers exploration based on orthogonal partial least squares-discriminant analysis

Zhenni Liu; Lizi Jin; Zijia Ma; Xiaerbanu Nizhamuding; Jie Zeng; Tianjiao Zhang; Jiangtao Zhang; Weiyan Zhou; Chuanbao Zhang

doi:10.1016/j.cca.2023.117531

Abnormal kynurenine-pathway metabolites in gout: Biomarkers exploration based on orthogonal partial least squares-discriminant analysis

Clin Chim Acta. 2023 Sep 1:549:117531. doi: 10.1016/j.cca.2023.117531. Epub 2023 Sep 4.

Authors

Zhenni Liu¹, Lizi Jin¹, Zijia Ma¹, Xiaerbanu Nizhamuding¹, Jie Zeng², Tianjiao Zhang¹, Jiangtao Zhang², Weiyan Zhou³, Chuanbao Zhang⁴

Affiliations

¹ National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
² National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China.
³ National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China. Electronic address: wyzhou@nccl.org.cn.
⁴ National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China. Electronic address: cbzhang@nccl.org.cn.

PMID: 37673380
DOI: 10.1016/j.cca.2023.117531

Abstract

Background: This study aims to investigate serological characteristics of kynurenine pathway (KP) metabolites in healthy controls (HC) and gout patients and explore possible differential metabolites.

Methods: A total of 191 individual fresh residual sera was collected from 129 HC and 62 gout patients. A liquid chromatography-tandem mass spectrometry method was fully validated to measure 6 metabolites, including tryptophan (TRP), kynurenine (KYN), 5-hydroxytryptamine (5HT), kynurenic acid (KA), xanthurenic acid (XA), and neopterin (NEO). Supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and differential metabolite screening with fold change (FC) were performed to identify intrinsic variations and differential levels of KP metabolites between the HC and gout groups. Logistic regression was used to assess the contributions of KP metabolites to gout.

Results: There were significant decreases of TRP, 5HT, XA, and NEO and increases of KYN, KA, KA/KYN, and KYN/TRP in gout patients compared to the HC group (all p < 0.05). KP metabolites of the gout group showed good discrimination from those of the HC group (Q²: 0.892). Two distinct different metabolites were identified in gout, i.e., XA (FC: 0.56, p < 0.01) and NEO (FC: 0.34, p < 0.01). Of the KP metabolites, KYN was strongly associated with gout (OR: 7.91, p < 0.01).

Conclusions: Abnormal levels of serum KP metabolites were observed in gout. XA and NEO are promising biomarkers that were relevant to the status of gout. The level of KYN could be an attractive checkpoint for the management of gout. Continuous monitoring of KP metabolism in gout provides new opportunities to predict therapeutic efficacy and prognosis.

Keywords: Biomarker; Gout; Kynurenine pathway; LC-MS/MS; Metabolites; Reference interval.