Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events.
Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events.
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DOI：
10.1111/j.1399-3046.2011.01485.x
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发表时间：
2011-05
影响因子：
1.3
通讯作者：
Garrett TJ
中科院分区：
文献类型：
--
作者：
Dharnidharka VR;Gupta S;Al Khasawneh E;Haafiz A;Shuster JJ;Theriaque DW;Shahlaee AH;Garrett TJ
感染已经成为与移植后急性排斥反应一样重要的事件，以保证移植物的长期存活。到目前为止，检测的侵入性较低的生物标志物预测了一种或另一种事件的风险，而不是两者。我们对接受肾移植的儿童在移植后12个月内每月进行一次血液和尿液的前瞻性检测。吲哚胺2，3双加氧酶（IDO）酶途径通过质谱分析使用产物L-犬尿氨酸（kyn）与底物色氨酸（trp）的比率进行评估。Kyn/trp比值和血CD 4 T细胞ATP水平与未来30天内的急性排斥反应或主要感染事件或稳定组（无事件）相关。25例受试者中5例发生了6次急性排斥反应，14例发生了16次重大感染事件（7例BK病毒尿，6例巨细胞病毒血症，1例EB病毒和巨细胞病毒血症，2例移植肾盂肾炎）。急性排斥组的平均血清kyn/trp比值显著升高（p = 0.02），受试者内分析显示，随着时间的推移，尿kyn/trp比值显示增加（p = 0.01），血液CD 4-ATP水平显示在重大感染事件之前下降（p = 0.007）。这些初步结果表明，一组生物标志物可以预测过度或免疫抑制不足，但需要独立验证。
Infections have become as important an event as acute rejection post-transplant 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 twelve months post-transplant from children receiving a kidney transplant. The indoleamine 2,3 dioxygenase (IDO) enzyme pathway was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (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 6 discrete episodes of acute rejection in 5 subjects and 16 discrete events of major infection in 14 subjects (7 BK viruria, 6 cytomegaloviremia, 1 Epstein-Barr and cytomegaloviremia, 2 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.
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影响因子：
6.2
作者：
Kowalski, Richard J.;Post, Diane R.;Britz, Judith A.
通讯作者：
Britz, Judith A.
影响因子：
4.4
作者：
FUCHS, D;MOLLER, AA;WACHTER, H
通讯作者：
WACHTER, H
影响因子：
3.7
作者：
Schroecksnadel, Katharina;Winkler, Christiana;Zangerle, Robert
通讯作者：
Zangerle, Robert
影响因子：
6.2
作者：
Dharnidharka, Vikas R.;Caillard, Sophie;Abbott, Kevin C.
通讯作者：
Abbott, Kevin C.
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL