Departments of Pathology and Laboratory Medicine, Vancouver, Canada; Medicine, University of British Columbia, Vancouver, Canada.
Departments of Pathology and Laboratory Medicine, Vancouver, Canada.
Hum Immunol. 2022 Mar;83(3):264-269. doi: 10.1016/j.humimm.2022.01.002. Epub 2022 Jan 31.
Advances in immunology support the understanding that precise structural epitopes on the antibody-accessible region of the HLA molecule determine antigenicity and challenge the need for identity across the full HLA molecule to minimize graft immunogenicity. Retrospective studies confirm that quantitative measurement of epitope-level mismatching between donor and recipient is an informative marker of graft rejection and survival and suggest that prospective allocation of donor organs based on this principle may improve graft survival. Here we describe the process for rigorous prospective evaluation of this hypothesis in a formal national proof-of-concept program for epitope-based matching. This encompasses broad societal consultation to engage the public, patients and providers; the development of clear allocation policies with strategies to support candidates who may be difficult to match; molecular and sequencing methods and web-based calculators enabling rapid epitope typing and recipient selection; precise immunological monitoring of the graft response; information systems permitting real-time monitoring of clinical outcomes; and assessment of health benefit and economic cost. The results of this objective evaluation can then be provided to payers and policy-makers for review, and adoption if of proven benefit.
免疫学的进展支持这样一种理解，即 HLA 分子抗体可及区域上精确的结构表位决定了抗原性，并对需要 HLA 分子完全匹配以最小化移植物免疫原性提出了挑战。回顾性研究证实，对供体和受者之间表位水平错配的定量测量是移植物排斥和存活的一个信息标志物，并表明基于这一原则对供体器官进行前瞻性分配可能会提高移植物的存活率。在这里，我们描述了在一个基于表位匹配的正式全国概念验证计划中，对这一假设进行严格前瞻性评估的过程。这包括广泛的社会咨询，以吸引公众、患者和提供者；制定明确的分配政策，并制定策略来支持那些可能难以匹配的候选人；分子和测序方法以及基于网络的计算器，可实现快速表位分型和受者选择；对移植物反应进行精确的免疫监测；信息系统可实时监测临床结果；并评估健康效益和经济成本。然后可以将这些客观评估的结果提供给支付者和决策者进行审查，如果证明有益，可以通过。
