Ahlenstiel-Grunow Thurid, Pape Lars
Department of Pediatrics II, University Hospital of Essen, University of Essen-Duisburg, Hufelandstraße 55, 45147, Essen, Germany.
Mol Cell Pediatr. 2021 Jul 26;8(1):8. doi: 10.1186/s40348-021-00118-8.
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.
小儿肾移植后，需进行免疫抑制治疗以避免急性和慢性排斥反应。然而，免疫抑制会增加严重病毒并发症和细菌感染的风险，并伴有严重的副作用。因此，在免疫抑制过度和不足之间实现最佳个体平衡，从而避免不必要地暴露于免疫抑制药物至关重要。在常规应用中，免疫抑制剂的调整主要通过监测反映药代动力学的谷浓度来进行（尽管不能反映药效动力学）。目前缺少评估个体免疫抑制强度的其他诊断和预后标志物。目前正在评估确定免疫功能和免疫抑制程度的潜在方法，如分析细小病毒（TTV）载量、QuantiFERON Monitor®、ImmuKnow®以及病毒特异性T细胞（Tvis）。在一些研究中，TTV载量、QuantiFERON Monitor®和ImmuKnow®与移植后排斥反应和感染风险相关，但尚无小儿肾移植后的随机对照试验。移植后监测Tvis水平似乎很有前景，因为Tvis可控制病毒复制，并已证明与病毒特异性以及一般细胞免疫防御相关，而细胞免疫防御代表个体对感染的易感性。额外的Tvis监测为小儿肾移植后个性化抗病毒管理和免疫抑制治疗剂量调整提供了创新机会，以避免不必要的治疗干预并识别免疫抑制过度。
