Accelerated kynurenine pathway downregulates immune activation in patients with axial spondyloarthritis

Various studies reported that the kynurenine (Kyn) pathway plays a pivotal role in regulating the balance between activation and inhibition of the immune system. Proinflammatory cytokines can accelerate the Kyn pathway by altering indoleamine (2, 3)- dioxygenase (IDO) allosteric enzyme activity. Excessive cytokine release and immune system activation have essential roles in the pathogenesis of axial spondyloarthritis (axSpA). We aimed to investigate the relationship of the Kyn pathway with proinflammatory cytokines and with the severity of the disease in patients with axSpA. The study included 104 patients with axSpA and 54 healthy volunteers. The severity of the disease was determined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Kyn pathway was evaluated by IDO activity calculated with Kyn/Tryptophan (Trp) ratio. Plasma Trp and Kyn concentrations were measured with tandem mass spectrometry. Serum IL 17/23 and IFN-? concentrations were measured with ELISA. These groups were compared in terms of IDO, IL-17, IL-23, IFN-?, and BASDAI. Plasma IDO activity was significantly increased, however, serum IL-17, IL-23, and IFN-? levels were significantly decreased in patients compared to healthy volunteers. While IFN-? was positively correlated with the severity of the disease (p = 0.02), it also had a significant inverse correlation with IDO activity (p < 0.001). However, these correlations are weak. As a result of this study, the Kyn pathway is accelerated and proinflammatory cytokine levels are decreased in patients with axSpA. All of these results with an indirect weak negative association between high IDO and low disease activity suggest that an accelerated Kyn pathway may limit the immune system activation in axSpA disease.

Automated summary

Various studies have shown that the Kyn pathway is important in regulating the immune system. In this study, it was found that the Kyn pathway is accelerated and proinflammatory cytokine levels are decreased in patients with axSpA.