Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis
Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis
复制标题
DOI：
10.1128/cvi.05402-11
复制
发表时间：
2012-03-01
影响因子：
--
通讯作者：
Chida, Kingo
中科院分区：
文献类型：
--
作者：
Suzuki, Yuzo;Suda, Takafumi;Chida, Kingo
结核病(TB)仍然是一个主要的健康问题，预测预后的生物标志物很少。吲哚胺2，3-双加氧酶(IDO)是一种强有力的免疫调节分子，在犬尿氨酸(Kyn)途径中催化色氨酸(Trp)降解的限速步骤。由血清Trp/Kyn比值确定的IDO活性的增加已被证明与癌症和菌血症的预后不良有关。然而，在结核病中，还没有研究通过测量血清IDO活性来确定其临床意义。采用高效液相色谱/电喷雾电离串联质谱仪对174例肺结核患者和85例正常对照的血清IDO活性进行了测定。通过计算血清Kyn/Trp比值来评估IDO活性。肺结核患者的KYN浓度和IDO活性显著高于对照组，色氨酸浓度显著低于对照组(P<；0.0001、P<；0.0001和P<；0.0001)。174例肺结核患者中，39例(22.4%)死亡。死亡患者的Kyn浓度显著升高，Trp浓度显著降低，导致IDO活性显著升高(分别为P<；0.0001、P<；0.0001和P<；0.0001)。在受试者操作特征(ROC)分析中，血清IDO活性曲线下面积最高(0.850)，在多因素分析中该活性是一个独立的预后因素。提示血清IDO活性可作为判断肺结核预后的新指标。
Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P < 0.0001, P < 0.0001, and P < 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.