监测儿童肾移植受者免疫抑制的新方法——基本概念和新数据。

IF 2.4 Q1 PEDIATRICS Molecular and cellular pediatrics Pub Date : 2021-07-26 DOI:10.1186/s40348-021-00118-8
Thurid Ahlenstiel-Grunow, Lars Pape
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引用次数: 2

摘要

小儿肾移植后,免疫抑制治疗是为了避免急性和慢性排斥反应。然而,免疫抑制导致严重病毒并发症和细菌感染的风险增加,并伴有严重的副作用。因此,在免疫抑制过度和免疫抑制不足之间实现最佳的个体平衡,从而避免不必要的免疫抑制药物暴露是至关重要的。在常规使用中,免疫抑制剂的控制主要是通过监测反映药代动力学的低谷水平来进行的(尽管不是药效学)。其他评估个体免疫抑制强度的诊断和预后标志物缺失。目前正在评估确定免疫功能和免疫抑制等级的潜在方法,例如分析转矩病毒(TTV)载量、QuantiFERON Monitor®和ImmuKnow®以及病毒特异性T细胞(Tvis)。在一些研究中,TTV负荷、QuantiFERON Monitor®和ImmuKnow®与移植后排斥反应和感染的风险相关,但没有儿童肾移植后的随机对照试验。移植后Tvis水平的监测似乎是有希望的,因为Tvis控制病毒复制,并已被证明与病毒特异性以及一般细胞免疫防御相关,这代表了个体对感染的易感性。额外的tvs监测提供了一个创新的机会,可以个性化儿童肾移植后的抗病毒管理和免疫抑制治疗的剂量,以避免不必要的治疗干预和识别过度免疫抑制。
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Novel ways to monitor immunosuppression in pediatric kidney transplant recipients-underlying concepts and emerging data.

After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual's susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.

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