Department of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Research net REDInREN 016/0009, Instituto Salud Carlos III, Madrid, Spain.
Front Immunol. 2021 Jan 25;11:618202. doi: 10.3389/fimmu.2020.618202. eCollection 2020.
Immunosuppressive drugs are widely used to treat several autoimmune disorders and prevent rejection after organ transplantation. However, intra-individual variations in the pharmacological response to immunosuppressive therapy critically influence its efficacy, often resulting in poor treatment responses and serious side effects. Effective diagnostic tools that help clinicians to tailor immunosuppressive therapy to the needs and immunological profile of the individual patient thus constitute a major unmet clinical need. assays that measure immune cell responses to immunosuppressive drugs constitute a promising approach to individualized immunosuppressive therapy. Here, we present the Immunobiogram, a functional pharmacodynamic immune cell-based assay for simultaneous quantitative measurement of a patient's immune response to a battery of immunosuppressive drugs. Peripheral blood mononuclear cells collected from patients are immunologically stimulated to induce activation and proliferation and embedded in a hydrogel mixture in which they are exposed to a concentration gradient of the immunosuppressants of interest. Analysis of samples from kidney transplant patients using this procedure revealed an association between the sensitivity of individual patients to the immunosuppressive regimen and their immunological risk of transplant rejection. Incorporation of the Immunobiogram assay into clinical settings could greatly facilitate personalized optimization and monitoring of immunosuppressive therapy, and study of the mechanisms underlying resistance to immunosuppressants.
免疫抑制剂被广泛用于治疗多种自身免疫性疾病，并预防器官移植后的排斥反应。然而，免疫抑制剂治疗的个体内药物反应的个体差异会严重影响其疗效，导致治疗反应不佳和严重的副作用。有效的诊断工具可以帮助临床医生根据个体患者的需求和免疫状况来调整免疫抑制剂治疗，因此这是一个尚未满足的主要临床需求。测量免疫细胞对免疫抑制剂反应的检测方法为个体化免疫抑制剂治疗提供了一个很有前途的方法。在这里，我们提出了免疫生物测定法（Immunobiogram），这是一种基于免疫细胞的功能性药效动力学检测方法，可同时定量测量患者对一系列免疫抑制剂的免疫反应。从患者中采集的外周血单核细胞被免疫刺激以诱导激活和增殖，并嵌入在水凝胶混合物中，使它们暴露于感兴趣的免疫抑制剂的浓度梯度中。使用该程序对肾移植患者的样本进行分析表明，个体患者对免疫抑制方案的敏感性与其移植排斥的免疫风险之间存在关联。将免疫生物测定法纳入临床环境可以极大地促进免疫抑制剂治疗的个性化优化和监测，并研究对免疫抑制剂产生耐药性的机制。
