Elevated serum levels of kynurenine pathway metabolites in patients with Behçet disease

Amino Acids. 2022 Jun;54(6):877-887. doi: 10.1007/s00726-022-03170-4. Epub 2022 May 23.

Abstract

Behçet disease (BD) is an inflammatory, multisystemic vasculitis of unknown etiopathogenesis. However, innate and adaptive immune system involvement and immune-mediated networks play a vital role in the inflammatory cascade. Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states and catalyzes the first and rate-limiting step of tryptophan (TRP) metabolism along the kynurenine pathway (KP). The study aimed to measure KP metabolites levels in patients with BD and investigate the relationship between disease activity and clinical findings with these metabolites. The study included 120 patients with BD and 120 healthy volunteers. Serum TRP, kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) levels were measured with the tandem mass spectrometric method. Demographic data, clinical manifestations, and disease activity score (BDCAF) were recorded. Serum KYN, KYNA, 3HK, 3HAA, QUIN levels, and KYN/TRP ratio were higher (p < 0.05) in patients with BD compared to the control group, while TRP levels were lower (p < 0.05). KYN/TRP ratio and QUIN levels were significantly higher in the presence of neuro-Behçet, while serum KYN levels were significantly higher in the presence of arthritis (p < 0.05). In addition, serum QUIN levels were significantly higher in the presence of thrombosis (p < 0.05). BDCAF score positively correlated with KYN/TRP ratio. Our findings showed that serum KP metabolite levels were elevated in patients with BD, and there is a relationship between these metabolites with disease activity, clinical findings, and inflammatory burden.

Keywords: Behçet disease; Immune regulation; Inflammation; Kynurenine pathway.

MeSH terms

  • Behcet Syndrome*
  • Humans
  • Kynurenic Acid / metabolism
  • Kynurenine*
  • Quinolinic Acid / metabolism
  • Tryptophan / metabolism

Substances

  • Kynurenine
  • Tryptophan
  • Quinolinic Acid
  • Kynurenic Acid