Tryptophan degradation increases with stage in patients with rheumatoid arthritis

Abstract

Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The proinflammatory cytokine interferon-gamma in various cells, including monocytes, induces the enzyme indoleamine (2,3)-dioxygenase (IDO), which converts tryptophan to kynurenine. In sera of 22 patients (17 women and 5 men) with RA stages 1 to 4 according to Steinbrocker, the concentrations of tryptophan and kynurenine were measured by high-pressure liquid chromatography. To estimate IDO activity, the kynurenine to tryptophan ratio (kyn/trp) was calculated. In parallel, concentrations of the macrophage activation marker neopterin were determined by enzyme-linked immunosorbent assay. Tryptophan concentrations were lower in patients with RA, and the decrease in serum tryptophan correlated with increase in stage (p<0.05). Kyn/trp correlated well with neopterin concentrations, which were elevated in most patients. Whereas higher C-reactive protein concentrations and erythrocyte sedimentation rates were observed in patients with greater disease activity, tryptophan and neopterin concentrations did not differ between patients with different subjective disease activity graded by the physician. Deficiency of the essential amino acid tryptophan in patients with RA most likely results from immune activation involved in the pathogenesis of the disease. It could also be relevant for the mood of patients, as tryptophan is the precursor of serotonin.

Myeloid differentiation primary response protein 88 blockade upregulates indoleamine 2,3-dioxygenase expression in rheumatoid synovial fibroblasts

“…Previous studies showed that exposure of synovial fibroblasts to IFN-γ caused a massive increase in IDO expression (Yuan et al, 1998). Moreover, IDO was activated in the synovial membrane of RA (Igari et al, 1987) and the decrease of tryptophan in serum of patients with RA correlated well with greater disease activity (Schroecksnadel et al, 2006). These findings suggest that certain factors in the inflammatory milieu of the joints in RA may induce high levels of IDO expression.…”

Tryptophan degradation in autoimmune diseases

“…For instance, in RA increased Trp degradation correlates with the progression of disease (RA stages 1-4 according to Steinbrocker) [82]. In patients with SLE, enhanced Trp degradation was found when serositis or decreased complement and blood counts (anaemia, leukopaenia, lymphopaenia) were present, but only a weak association between Trp degradation and the SLE disease activity index (SLEDAI) was observed [84].…”

“…Patients with rheumatoid arthritis (RA) [80][81][82], systemic lupus erythematosus (SLE) [83,84] and primary Sjçgren's Syndrome (pSS) [85] display significantly decreased blood levels of Trp as well as increased levels of kynurenine in comparison with healthy controls. In addition, decreased 3-hydroxykynurenine and 3-hydroxyanthranilic acid as well as increased xanthurenic acid were detected in patients with RA in comparison to healthy controls, while kynurenic acid concentrations remained normal [80].…”

Tryptophan and Indoleamine-2,3-Dioxygenase (Ido) in Pathogenesis of Immunosuppressive Clinical Conditions

“…Описано значимое увеличение отношения Кин/ Три при РА. При этом снижение концентра-ции триптофана ассоциировалось с прогрессив-ной стадией заболевания, но не с активностью, со степенью которой лучше коррелировали по-казатели СРБ и СОЕ [69]. Авторы предполагают, что супрессивных механизмов, индуцирован-ных катаболизмом Три, не достаточно, чтобы полностью заингибировать аутоиммунный про- [85].…”