Serum tryptophan-kynurenine metabolites served as biomarkers of disease activity in rheumatoid arthritis and linked to immune imbalance

作者：Ruihe Wu, Baochen Li, Rui Su, Xiaoyang Liu, Anqi Gao, Jing Luo, Chong Gao, Xiaofeng Li, Caihong Wang · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03596-7 · 被引用次数：11 · 研究领域：Tryptophan and brain disorders、Rheumatoid Arthritis Research and Therapies、Metabolomics and Mass Spectrometry Studies

BACKGROUND: Immune imbalance caused by imbalanced helper T(Th)17/regulatory T (Treg) and follicular helper T (Tfh)/follicular regulatory T (Tfr) cells drives the onset of rheumatoid arthritis (RA) fundamentally. Tryptophan (Trp) metabolism is crucial in regulating immune and altered Trp metabolism has been reported in RA. However, the potential of altered Trp metabolites to serve as RA-related biomarkers and their relationship to immune balance in RA remains undetermined. METHODS: We explored the Trp metabolic characteristics in RA by comparing the targeted quantitative Trp metabolomics between 29 new-onset RA patients and 19 healthy controls (HCs). The RA-related disease biomarkers from Trp metabolites were identified to construct a classification model through machine learning algorithms. Their association with immune imbalance in RA was analyzed. RESULTS: Differential analysis exhibited significant alterations in serum Trp metabolites and metabolic pathways between RA and HCs. There were 7 differential metabolites of serum Trp, which were all decreased in RA (P < 0.05). Trp metabolic pathways analysis indicated that the Trp-Kynurenine(Kyn) pathway was downregulated in RA(P < 0.05). And the key enzyme of the Trp-Kyn pathway, indoleamine-2,3-dioxygenase1 (IDO1), was reduced in RA (P < 0.05). Altered Trp metabolites especially those from the Trp-Kyn pathway exhibited a negative correlation with the clinical indicators and autoantibody expression. 4 Trp metabolites from the Tr...