Al Khasawneh Eihab, Gupta Sushil, Tuli Sanjeev Y, Shahlaee Amir H, Garrett Timothy J, Schechtman Kenneth B, Dharnidharka Vikas R
College of Medicine, University of Florida, Gainesville, FL, USA.
Pediatr Transplant. 2014 May;18(3):254-7. doi: 10.1111/petr.12232. Epub 2014 Feb 1.
Immune cells utilize the IDO enzymatic conversion of trp to kyn to determine T-cell activation vs. anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here, we analyzed the difference between urine IDO levels in stable post-transplant vs. healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one-time urine samples, from 34 well children at general pediatric clinics, to the first-month post-transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first-month post-kidney transplant (median 16.6, range 3.9-44.0) vs. healthy children (median 9.2, range 3.51-17.0; p = 0.0057 by nonparametric Mann-Whitney test). Higher urine IDO levels even with stable transplant suggest a continuous ongoing low-grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies.
免疫细胞利用吲哚胺2,3-双加氧酶(IDO)将色氨酸(trp)酶促转化为犬尿氨酸(kyn)来决定T细胞的激活与无反应性/凋亡。在先前的研究中,正在发生排斥反应的肾移植受者尿液中的IDO水平高于稳定状态者。然而,健康受试者或儿童的尿液IDO水平尚不清楚。作为一项关于血清和尿液IDO水平用于移植免疫监测的更大规模纵向前瞻性研究的一个必然结果,在此我们分析了移植后处于稳定状态的儿童与健康儿童尿液IDO水平的差异。通过串联质谱法测量IDO水平,并以犬尿氨酸/色氨酸比值表示。我们将普通儿科门诊34名健康儿童的一次性尿液样本与18名处于稳定状态(未来30天内无急性排斥反应或重大感染事件)的儿童移植后第一个月的尿液样本进行了比较。肾移植后第一个月稳定状态儿童的尿液犬尿氨酸/色氨酸比值(中位数16.6,范围3.9 - 44.0)显著高于健康儿童(中位数9.2,范围3.51 - 17.0;非参数曼-惠特尼检验p = 0.0057)。即使移植处于稳定状态,较高的尿液IDO水平也提示存在持续的低级别同种异体识别/炎症过程。我们的数据还提供了健康受试者的尿液IDO基线水平,以供未来研究使用。