IDO/TTS比值在RA排除及病情评估中的价值

Role of IDO/TTS ratio in the exclusion and disease assessment of RA

目的探讨吲哚胺2,3双加氧酶(IDO)/色胺酰-tRNA合成酶(TTS)比值在类风湿性关节炎(RA)中的临床意义。方法选取88例RA患者(RA组)和88名体检健康者(正常对照组),采用高效液相色谱法检测血浆犬尿氨酸(Kyn)和色氨酸(Trp)水平,并计算Kyn/Trp比值,采用流式细胞术测定淋巴细胞中IDO和TTS的表达并计算IDO/TTS比值;采用荧光定量逆转录-聚合酶链反应(RT-PCR)检测外周血单个核细胞(PBMC)IDO mRNA、TTS mRNA的相对表达量并计算IDO mRNA/TTS mRNA比值。根据改良疾病活动指数28(DAS28)评分将RA患者分为低活动度组(35例,DAS28评分≤3.2分)、中活动度组(42例,DAS28评分为>3.2分~≤5.1分)和高活动度组(11例,DAS28评分>5.1分)。采用受试者工作特征(ROC)曲线评估IDO/TTS比值在RA排除及病情评估中的价值。结果 RA组血浆Kyn、Trp水平及淋巴细胞TTS的表达量、TTS mRNA的相对表达量均高于正常对照组(P=0.000),Kyn/Trp比值、淋巴细胞IDO的表达量、IDO/TTS比值、IDO mRNA的相对表达量和IDO mRNA/TTS mRNA比值均低于正常对照组(P=0.000)。低活动度组、中活动度组及高活动度组之间IDO/TTS比值依次降低,各组间差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,IDO/TTS比值排除RA的曲线下面积(AUC)为0.841,最佳临界值为0.080,敏感性为84.2%,特异性为81.6%,阴性预测值为0.838,阳性预测值为0.821;判断RA病情严重程度的AUC为0.734,最佳临界值为0.042,敏感性为72.1%,特异性为70.7%,阴性预测值为0.626,阳性预测值为0.788。结论 IDO/TTS比值可用于排除RA,对评估RA病情也有较高的价值。

Objective To investigate the roles of indoleamine 2,3-dioxygenase(IDO)/tryptophanyl-tRNAsynthetase(TTS)ratio in rheumatoid arthritis(RA).Methods 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 predictivevalue was 0.838,and the positive predictive value was 0.821. The AUC in the disease assessment of RA was 0.734,theoptimal cut-off value was 0.042,the sensitivity was 72.1%,the specificity was 70.7%,the negative predictive valuewas 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.