Investigation of complex dynamics of donor specific antibodies in high risk kidney transplantation. Category Control engineering and Healthcare tech

肾功能衰竭是世界范围内增长最快的死亡诱因之一。由于缺乏负担得起的治疗，只有10%的患者得到治疗，每年有100万人死亡。肾功能衰竭的最佳治疗方法是肾移植，理想情况下，当一个兼容的供体可用时进行。提供兼容的肾脏移植是一项挑战，导致超过一半的患者平均等待2.5年才能得到治疗。幸运的是，在过去的几十年里，不相容的肾移植已经有了很大的发展。诊断和测定技术的进步允许在HLA抗体存在下进行移植。然而，临床结果的预测仍然具有挑战性。针对供体特异性抗体（DSA）的特性进行了大量的研究。然而，确定特异性DSA抗体的影响才刚刚开始。特别是，在最近的研究中，首次研究了移植后早期总DSA的动态。应用无监督机器学习将DSA反应聚类为五组（无反应、快速调节、缓慢调节、上升至持续和持续）。研究结果表明，快速调节动力学与早期急性排斥反应率的增加（80%）高度相关，与持续组相反，持续组与最低的肾排斥反应率（19%）相关。相比之下，移植后早期的调节反应对长期移植结果具有保护作用。该项目旨在进一步研究DSA动态模式，强调DSA特异性反应并将其与移植结果联系起来。该项目的成功将有助于HLA不相容移植领域，为数百万等待相容供体的患者提供希望。控制

Renal failure is one of the fastest-rising death triggers worldwide. Due to the lack of affordable treatment, only 10% of patients receive treatment, and a million die yearly. The optimal treatment for renal failure is a kidney transplant, ideally performed when a compatible donor is available. Providing a compatible kidney transplant is challenging, resulting in more than half of patients waiting an average of 2.5 years to get treatment. Luckily, incompatible kidney transplant has evolved significantly in the last few decades. Advancement in diagnoses and assay techniques allows for transplantation in the presence of HLA antibodies. However, the prediction of clinical outcomes is still challenging. A lot of research has been carried out focusing on the characteristics of donor-specific antibodies (DSA). Yet, determining the impact of specific DSA antibodies is only just undertaken. In particular, in recent studies, the dynamic of total DSA during the early post-transplant period was investigated for the first time. Unsupervised machine learning was applied to cluster the DSA responses into five groups (no response, fast modulation, slow modulation, rise to sustained and sustained). The research findings suggested that fast modulation dynamics are highly related to the increasing rate of early acute rejection (80%), opposite to the sustained group that showed an association with the lowest kidney rejection rates (19%). In contrast, modulated response in the early post-transplant period was protective for a long-term graft outcome. This project aims to investigate the DSA dynamic patterns further, emphasising DSA-specific responses and linking them to the transplantation outcome. The success of this project will contribute to the area of HLA incompatible transplants, which provides hope for millions of patients waiting for a compatible donor. Control