HIGH ACTIVITY OF INDOLEAMINE 2,3 DIOXYGENASE ENZYME PREDICTS DISEASE SEVERITY AND CASE FATALITY IN BACTEREMIC PATIENTS
HIGH ACTIVITY OF INDOLEAMINE 2,3 DIOXYGENASE ENZYME PREDICTS DISEASE SEVERITY AND CASE FATALITY IN BACTEREMIC PATIENTS
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DOI：
10.1097/shk.0b013e3181ad3195
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发表时间：
2010-02-01
期刊：
影响因子：
3.1
通讯作者：
Hurme, Mikko
中科院分区：
文献类型：
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作者：
Huttunen, Reetta;Syrjanen, Jaana;Hurme, Mikko
吲哚胺2，3-双加氧酶(IDO)是色氨酸(Trp)分解代谢的限速酶，可能在多种炎症性疾病中发挥重要作用。最近对创伤患者的研究表明，Trp的降解与脓毒症的发生有关。IDO活性在菌血症患者中的作用尚不清楚。本文对132例金黄色葡萄球菌、肺炎链球菌、P-溶血性链球菌、大肠埃希菌引起的菌血症患者的IDO活性进行了研究。于阳性血培养后1~4d及恢复时，用反相高效液相色谱法测定血清色氨酸及其代谢物犬尿氨酸(KYN)浓度。计算反映IDO酶活性的Kyn/Trp比值(Kyn/Trp)。取每例患者血培养阳性后1~4d内的比值最大值进行分析。死亡组最大KYN/Trp比值显著高于存活组(193.7比82.4umol/mmo1；P=0.001)。最大KYN/Trp在预测病死率方面的AUC(ROC)为0.75(95%可信区间，0.64~0.87)，KYN/Trp比值在120mU/mol/mmo1的临界值时，对致死性疾病的敏感性为83%，特异性为69%。KYN/Trp比值大于120mU/mmoL/mmo1与死亡风险增加相关(
Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, P-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 mu mol/mmol; P = 0.001). The AUC(ROC) of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 mu mol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 mu mol/mmol was associated with increased risk of death versus low (