Disruptive technologies for rapid detection of renal transplant rejection

肾移植是治疗终末期肾衰竭的最有效方法，在欧盟有超过50万人受到影响；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。早期检测对于最大限度地发挥移植物的功能和改善移植患者的生活质量至关重要。目前，肾移植监测是通过侵入性活组织检查或无法具体报告急性移植排斥反应的测试进行的。需要非侵入性技术，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。这种未得到满足的患者需求推动了RENO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动的荧光化学工具箱。器官移植后，免疫细胞的活性反映了患者对移植器官的反应。颗粒酶B是一种在急性移植排斥反应中由过度激活的免疫细胞分泌的蛋白质，尿中颗粒酶B的高水平与肾脏排斥反应的早期阶段和疾病的严重程度有关。我们建议开发一种简单的方法来实时检测尿液中的活性颗粒酶B。这一测试将使我们能够及早识别急性排斥反应，减少侵入性活检的需要，并鼓励迅速进行治疗，以延长患者的肾移植生命。为该项目提供资金将使我们能够：1)通过向业界授权，将我们用于生物医学研究的荧光试剂商业化；2)为护理点式技术奠定基础，以测量肾移植患者尿液中颗粒酶B的活性。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，并将为加快肾脏排斥反应的研究、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.