Abstract:

Objective To investigate the roles of indoleamine 2,3-dioxygenase（IDO）/tryptophanyl-tRNA-synthetase（TTS） ratio in rheumatoid arthritis（RA）. Methodse A total of 88 patients with RA（RA group） and 88 healthy subjects（healthy control group） were enrolled. Kynurenine（Kyn） and tryptophan（Trp） levels in plasma were determined by high performance liquid chromatography,and the Kyn/Trp ratio was calculated. Flow cytometry was used to determine the expressions of IDO and TTS in lymphocytes,and the IDO/TTS ratio was calculated. Fluorescence quantitative reverse transcription-polymerase chain reaction（RT-PCR） was used to determine peripheral blood mononuclear cells（PBMC）. The relative expressions of IDO mRNA and TTS mRNA were determined,and the ratio of IDO mRNA/TTS mRNA was calculated. According to the improved disease activity score 28（DAS28）,RA patients were classified into low activity group（DAS28≤3.2 points,35 cases）,medium activity group（DAS28>3.2-≤5.1 points,42 cases） and high activity levels（DAS28>5.1 points,11 cases）. Receiver operating characteristic（ROC） curve was used to evaluate the role of IDO/TTS ratio in the exclusion and disease assessment of RA. Results The levels of Kyn and Trp in plasma,the expression of TTS in lymphocytes and the relative expression of TTS mRNA in RA group were higher than those in healthy control group（P=0.000）,and the ratio of Kyn/Trp,the expression of IDO in lymphocytes,IDO/TTS ratio,the relative expression of IDO mRNA and the ratio of IDO mRNA/TTS mRNA were lower than those in healthy control group（P=0.000）. The IDO/TTS ratio of low activity group,medium activity group and high activity group decreased in order,and there was statistical significance among the groups（P<0.05）. ROC curve analysis showed that the area under curve（AUC） of IDO/TTS ratio in the exclusion of RA was 0.841,and the optimal cut-off value was 0.080,the sensitivity was 84.2%,and the specificity was 81.6%,the negative predictive value was 0.838,and the positive predictive value was 0.821. The AUC in the disease assessment of RA was 0.734,the optimal cut-off value was 0.042,the sensitivity was 72.1%,the specificity was 70.7%,the negative predictive value was 0.626,and the positive predictive value was 0.788. Conclusions The IDO/TTS ratio can be used to exclude RA,and also has a value for assessing RA.

Key words: Indoleamine 2, 3-dioxygenase, Tryptophanyl-tRNA-synthetase, Rheumatoid arthritis