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Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors would like to thank the Selcuk University for this study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Each named author has substantially contributed to conducting the research and drafting the manuscript.

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Correspondence to Duygu Eryavuz Onmaz.

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The authors declare no competing interest.

Ethical approval

This study was performed according to guidelines established by the 2013 Helsinki Declaration and protocol was approved by Selcuk University Faculty of Medicine Ethics Committee (Number: 2021/280, Date: 26.05.2021).

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Handling editor: D. Tsikas.

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Eryavuz Onmaz, D., Tezcan, D., Yilmaz, S. et al. Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus. Amino Acids 55, 1937–1947 (2023). https://doi.org/10.1007/s00726-023-03353-7

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  • DOI: https://doi.org/10.1007/s00726-023-03353-7

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