Increased degradation of tryptophan in blood of patients with rheumatoid arthritis.
OBJECTIVE
Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response.


METHODS
Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity.


RESULTS
Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02-48.60 mM/M) than in controls (31.72 mM/M; 27.95-35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA.


CONCLUSIONS
The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA.
Schroecksnadel
Katharina
K
Institute of Medical Chemistry and Biochemistry, Leopold Franzens University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.
Kaser
Sabine
S
Ledochowski
Maximilian
M
Neurauter
Gabriele
G
Mur
Erich
E
Herold
Manfred
M
Fuchs
Dietmar
D
D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000032:analysis / Q000378:metabolism*; D008297:Male; D019798:Neopterin / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan