The kynurenine pathway in patients with rheumatoid arthritis during tumor necrosis factor α inhibitors treatment.

Introduction: The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA.

Material and methods: This was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynurenine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated.

Results: The results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynurenine-to-tryptophan ratio (p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors (p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation.

Conclusions: The RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA - especially for comorbidity of RA and depression.