Mehrotra Anita, Leventhal Jeremy, Purroy Carolina, Cravedi Paolo
Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, NY, USA.
Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, NY, USA.
Transplant Rev (Orlando). 2015 Apr;29(2):53-9. doi: 10.1016/j.trre.2014.11.001. Epub 2014 Nov 12.
Currently, immunosuppressive therapy in kidney transplant recipients is center-specific, protocol-driven, and adjusted according to functional or histological evaluation of the allograft and/or signs of drug toxicity or infection. As a result, a large fraction of patients receive too much or too little immunosuppression, exposing them to higher rates of infection, malignancy and drug toxicity, or increased risk of acute and chronic graft injury from rejection, respectively. The individualization of immunosuppression requires the development of assays able to reliably quantify and/or predict the magnitude of the recipient's immune response toward the allograft. As alloreactive T cells are central mediators of allograft rejection, monitoring T cell alloreactivity has become a priority for the transplant community. Among available assays, flow cytometry based phenotyping, T cell proliferation, T cell cytokine secretion, and ATP release (ImmuKnow), have been the most thoroughly tested. While numerous cross-sectional studies have found associations between the results of these assays and the presence of clinically relevant post-transplantation outcomes, data from prospective studies are still scanty, thereby preventing widespread implementation in the clinic. Future studies are required to test the hypothesis that tailoring immunosuppression on the basis of results offered by these biomarkers leads to better outcomes than current standard clinical practice.
目前,肾移植受者的免疫抑制治疗是由各中心特定的、遵循方案驱动的,并根据同种异体移植物的功能或组织学评估和/或药物毒性或感染迹象进行调整。因此,很大一部分患者接受的免疫抑制过多或过少,分别使他们面临更高的感染、恶性肿瘤和药物毒性发生率,或因排斥反应导致急性和慢性移植物损伤的风险增加。免疫抑制的个体化需要开发能够可靠地量化和/或预测受者对同种异体移植物免疫反应强度的检测方法。由于同种异体反应性T细胞是同种异体移植物排斥反应的核心介质,监测T细胞同种异体反应性已成为移植界的首要任务。在现有的检测方法中,基于流式细胞术的表型分析、T细胞增殖、T细胞细胞因子分泌和ATP释放(ImmuKnow)检测是经过最全面测试的。虽然众多横断面研究发现这些检测结果与临床上相关的移植后结局之间存在关联,但前瞻性研究的数据仍然很少,从而阻碍了这些检测方法在临床上的广泛应用。未来需要进行研究,以验证基于这些生物标志物提供的结果来调整免疫抑制方案是否比当前标准临床实践能带来更好的结局这一假设。