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

高风险肾移植中供体特异性抗体复杂动态的研究。

• 批准号: 2871808
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2871808
• 关键词: Investigation; complex; dynamics; donor; specific

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

肾功能衰竭是全球上升最快的死亡诱因之一。由于缺乏负担得起的治疗，只有10%的患者接受治疗，每年有100万人死亡。肾功能衰竭的最佳治疗方法是肾移植，最好是在有相容供者的情况下进行。提供相容的肾脏移植是具有挑战性的，导致超过一半的患者平均等待2.5年才能获得治疗。幸运的是，在过去的几十年里，血型不合的肾移植已经发生了显著的变化。诊断和检测技术的进步允许在存在人类白细胞抗原抗体的情况下进行移植。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)的特性已经开展了大量的研究。然而，确定特定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的动态变化。应用无监督机器学习将DSA响应分为5组(无响应、快速调制、慢调制、上升为持续和持续)。研究结果表明，快速调制动力学与早期急性排斥反应的增加(80%)高度相关，而持续组与最低的肾排斥反应发生率(19%)相反。相反，移植后早期的调制反应对移植的长期结果具有保护作用。该项目旨在进一步研究DSA的动态模式，强调DSA特异性的反应，并将它们与移植结果联系起来。该项目的成功将有助于人类白细胞抗原血型不合的移植领域，这为数百万等待相合捐赠者的患者带来了希望。控制