Abstract
Abstract
Objectives
Extrahepatic tryptophan (Trp)-kynurenine (Kyn) metabolism via indoleamine 2,3-dioxygenase 1 (IDO1) induction was found to be associated with intrinsic immune regulation. However, the Trp-Kyn metabolism–associated immune regulation in dermatomyositis (DM) remains unknown. Therefore, we aimed to investigate the clinical relevance of the Trp-Kyn metabolism via IDO1 induction in DM.
Methods
Liquid chromatography-mass spectrometry (HPLC–MS) was used to examine the serum Kyn and Trp concentrations in DM. In addition, we used X-tile software to determine the optimal cutoff value of the Kyn/Trp ratio, a surrogate marker for Trp-Kyn metabolism. Spearman analysis was performed to evaluate the association of Trp-Kyn metabolism with muscle enzymes and inflammatory markers.
Results
DM patients had significantly higher serum Kyn/Trp ratio (× 10−3) when compared with the healthy controls. The serum Kyn/Trp ratio was positively correlated with the levels of muscle enzymes and inflammatory markers. In addition, the serum Kyn/Trp ratio significantly decreased (36.89 (26.00–54.00) vs. 25.00 (18.00–37.00), P = 0.0006) after treatment. DM patients with high serum Kyn/Trp ratio had a significantly higher percentage of muscle weakness symptoms (62.5% vs. 20.0%, P = 0.019) and higher levels of LDH (316.0 (236.0–467.0) vs. 198.0 (144.0–256.0), P = 0.004) and AST (56.5 (35.0–92.2) vs. 23.0 (20.0–36.0), P = 0.002)) than those with low serum Kyn/Trp ratio. Multiple Cox regression analyses identified ln(Kyn/Trp) (HR 4.874, 95% CI 1.105–21.499, P = 0.036) as an independent prognostic predictor of mortality in DM.
Conclusions
DM patients with enhanced Trp-Kyn metabolism at disease onset are characterized by more severe disease status and poor prognosis. Intrinsic immune regulation function via enhanced Trp-Kyn metabolism by IDO1 induction may be a potential therapeutic target in DM.
Key Points• HPLC–MS identified increased serum Kyn/Trp ratio in DM patients, which positively correlated with levels of muscle enzymes and inflammatory markers and was downregulated upon treatment.• Cox regression analyses identified ln(Kyn/Trp) as an independent prognostic predictor of mortality in DM.• Monitoring intrinsic immune regulation function should be considered a potential therapeutic target in DM patients.
Funder
National Natural Science Foundation of China
Clinical Research Plan of SHDC
National Key Clinical Specialty
Shanghai Municipal Commission of Economy and Informatization
Science and Technology Commission of Shanghai Municipality
Shanghai Yiyuan Rising Star Outstanding Young Medical Talents
Publisher
Springer Science and Business Media LLC
Subject
General Medicine,Rheumatology
Cited by
2 articles.
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