Dharnidharka Vikas R, Gupta Sushil, Al Khasawneh Eihab, Haafiz Allah, Shuster Jonathan J, Theriaque Douglas W, Shahlaee Amir H, Garrett Timothy J
Division of Pediatric Nephrology, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA.
Pediatr Transplant. 2011 May;15(3):321-8. doi: 10.1111/j.1399-3046.2011.01485.x. Epub 2011 Feb 24.
Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.
对于长期同种异体移植存活而言，感染已成为与移植后急性排斥反应同样重要的事件。迄今为止所检测的侵入性较小的生物标志物只能预测其中一种事件的风险，而非两种事件的风险。我们对接受肾移植的儿童在移植后12个月每月进行血液和尿液检测。通过质谱分析使用产物l-犬尿氨酸与底物色氨酸的比率来评估吲哚胺2,3-双加氧酶（IDO）酶途径。犬尿氨酸/色氨酸比率和血液CD4 T细胞ATP水平与接下来30天内的急性排斥反应或严重感染事件或稳定组（无事件）相关。25名受试者中，5名受试者经历了6次离散的急性排斥反应发作，14名受试者经历了16次离散的严重感染事件（7例BK病毒尿症、6例巨细胞病毒血症、1例EB病毒和巨细胞病毒血症以及2例移植后肾盂肾炎）。经历急性排斥反应的组中，血清犬尿氨酸/色氨酸平均比率显著升高（p = 0.02）。受试者内分析显示，在严重感染事件发生前，随着时间推移，尿犬尿氨酸/色氨酸比率升高（p = 0.01），血液CD4-ATP水平降低（p = 0.007）。这些初步结果表明，一组生物标志物共同作用可以预测免疫抑制过度或不足，但需要独立验证。
