Individualization of Immunosuppressive Therapy Using Pharmacodynamics, Immunology and Molecular Biology

为了优化个体患者的免疫抑制治疗，已经提出了许多生物标记物，但关于与临床结果数据相关的信息很少。在器官移植中，最有效的免疫抑制策略是基于钙调神经磷酸酶抑制剂对IL-2信号的抑制，我们首先用RT-PCR方法评估了每个患者对IL-2mRNA产生的抑制。然后，我们用CFSE标记的流式细胞术检测个体T细胞对每种免疫抑制剂(环孢素、他克莫司、霉酚酸、强的松龙)的敏感性。对环孢素高度敏感的患者往往会经历病毒重新激活。移植前的药效学可以为最佳和安全的免疫抑制治疗提供有用的信息。

To optimize immunosuppressive treatment in individual patients, many biomarkers have been proposed, but there has been very little information about association to clinical outcome data. The most effective immunosuppressive strategies in organ transplantation are based on the inhibition of IL-2 signal by calcineurin inhibitiors and we first evaluated the inhibition of IL-2 mRNA production for each patient by using RT-PCR method. Then we examined individual T-cell sensitivity to each immunosuppressive agent (cyclosporine, tacrolimus, mycophenolic acid, predonisolone) using flow cytometry with CFSE labeling. Patients with high sensitivity to cyclosporine tended to experience viral reactivation. Pretransplant pharmacodynamics could provide useful information on optimal and safe immunosuppressive therapy.