Altered kynurenine pathway metabolism in patients with ankylosing spondylitis

Int Immunopharmacol. 2021 Oct:99:108018. doi: 10.1016/j.intimp.2021.108018. Epub 2021 Aug 3.

Abstract

Background: Various studies reported that increased proinflammatory cytokines in patients with ankylosing spondylitis (AS). Proinflammatory cytokines can affect the expression of various kynurenine pathway enzymes and therefore lead to metabolic changes that can affect the inflammatory response and immunity. Our aim was to measure serum levels of kynurenine pathway metabolites in patients with AS.

Methods: The study included 85 patients with AS and 50 healthy volunteers. Serum tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, quinolinic acid concentrations were measured with tandem mass spectrometry. In addition, participants were divided into four groups according to the treatment regimen: TNF-α inhibitor group, conventional therapy group, control group and newly diagnosed AS group. These groups were compared in terms of kynurenine pathways metabolites, interleukin 6 (IL-6), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

Results: Serum tryptophan, kynurenic acid, 3-hydroxykynurenine levels were significantly decreased (p < 0.05) in both AS groups compared to the control group, while the levels of kynurenine, quinolinic acid, CRP, ESR, and IL-6 were higher (p < 0.05). The Kynurenine/Tryptophan ratio and CRP levels of the conventional therapy and anti-TNF therapy group were significantly lower than the newly diagnosed AS patients (p < 0.05).

Conclusion: As a result of our study, we found that altered kynurenine pathway metabolism in patients with AS. Conventional therapy and anti-TNF-α therapy are effective in reducing the Kynurenine/Tryptophan ratio and CRP levels, although the effect of both treatments on other metabolites appears to be limited.

Keywords: Ankylosing spondylitis; Inflammation; Kynurenine; Tryptophan.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Kynurenine / blood
  • Kynurenine / metabolism*
  • Male
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / immunology
  • Middle Aged
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / metabolism
  • Tryptophan / blood
  • Tryptophan / metabolism*
  • Tumor Necrosis Factor Inhibitors / pharmacology*
  • Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor Inhibitors
  • Kynurenine
  • Tryptophan
  • C-Reactive Protein