Disruptive technologies for rapid detection of renal transplant rejection

肾移植是终末期肾衰竭最有效的治疗方法，在欧盟影响超过50万人;然而，三分之一的患者可能在接受移植的第一年内经历急性排斥反应。早期发现对于最大限度地发挥移植物功能和改善移植患者的生活质量至关重要。目前，肾移植监测是用侵入性活检或不能特异性报告急性移植排斥反应的测试进行的。需要能够快速测量急性器官排斥反应并监测疾病进展和对治疗的反应的非侵入性技术。这种未满足的患者需求推动了里诺项目的发展。ERC CoG项目DYNAFLUORS提供了第一个用于成像免疫细胞活性的荧光化学工具箱。器官移植后，免疫细胞的活性指示患者对移植器官的反应。颗粒酶B是在急性移植排斥期间由过度活化的免疫细胞分泌的蛋白质，尿中高水平的颗粒酶B与肾排斥的早期阶段和疾病严重程度相关。我们建议开发一个简单的测试来测量活性颗粒酶B在尿液中的真实的时间。这项测试将有助于早期识别急性排斥反应，减少对侵入性活检的需要，并鼓励及时治疗，以延长患者的肾移植寿命。该项目的资助将使我们能够：1）通过与行业的许可，将我们的荧光试剂商业化用于生物医学研究，和2）建立床旁技术的基础，以测量经历肾移植的患者的尿液中的颗粒酶B活性。该项目将以现有和新的工业和临床合作伙伴的投入为指导，并将为加速肾排斥反应的研究、早期发现和有效治疗创造机会。

Kidney transplantation is the most effective treatment for end-stage kidney failure, which affects over 0.5 million people in the EU; however, 1 in 3 patients may experience acute rejection within the first year of receiving a transplant. Early detection is critical to maximize graft function and improve the quality of life for patients with transplants. Currently, renal transplant monitoring is performed with invasive biopsies or with tests that cannot specifically report on acute transplant rejection. There is a need for noninvasive technologies that can rapidly measure acute organ rejection and monitor disease progression and response to therapy. This unmet patient need drives the development of the project RENO.The ERC CoG project DYNAFLUORS delivered the first fluorescent chemical toolbox for imaging immune cell activity. After organ transplantation, the activity of immune cells is indicative on how patients respond to the transplanted organ. Granzyme B is a protein secreted by over-activated immune cells during acute transplant rejection, with high levels of granzyme B in urine correlating to early stages of kidney rejection and with disease severity. We propose to develop a simple test to measure active granzyme B in urine in real time. This test will enable early identification of acute rejection, reduce the need for invasive biopsies, and encourage prompt treatment to prolong the life of a renal transplant for patients.Funding for this project will allow us to: 1) commercialize our fluorescent reagents for biomedical research through licensing with industry, and 2) establish the foundations for point-of-care technologies to measure granzyme B activity in the urine of patients that have undergone renal transplantation. This project will be guided by input from existing and new industrial and clinical partners, and will create opportunities for accelerating the research, early detection and effective treatment of kidney rejection.