Tissue Typing Laboratory (GHATT), University Hospital, Martin-Luther University Halle-Wittenberg, Germany.
Institute of Biology/Microbiology, Martin-Luther University Halle-Wittenberg, Germany.
Histol Histopathol. 2020 Sep;35(9):937-948. doi: 10.14670/HH-18-217. Epub 2020 Apr 15.
Transplant recipients who have undergone sensitizing events, such as pregnancy, blood transfusion or previous transplants, frequently develop antibodies directed against the highly polymorphous human leukocyte antigen (HLA)-molecules. These pre-formed, donor-specific antibodies (DSA) present a high risk of causing organ failure or even complete loss of the grafted organ as a consequence of antibody-mediated, hyper-acute or acute allograft rejection. In order to detect DSA, the so-called functional complement-dependent lymphocytotoxicity assay (CDC-XM) was established about 50 years ago. Although effective in improving the outcome of solid organ allo-grafting, for the last ten years this assay has been controversially discussed due to its low sensitivity and especially because of its high susceptibility to various artificial factors, which generally do not yield reliable results. As a consequence, novel immunochemical test systems have been developed using ELISA- or bead-based solid phase assays as replacements for the traditional CDC-based assays. Because these assays are independent of single or vital cells, which are frequently not available, they have provided an additional and alternative diagnostic approach compared with the traditional CDC-based and flow-cytometric analyses. Unfortunately, however, the AMS-ELISA (Antibody Monitoring System), which was the first system to become commercially available, was recently discontinued by the manufacturer after seven years of successful use. Alternative procedures, such as the AbCross-ELISA, had to be either considerably modified, or did not yield reliable results, as in the case of the Luminex-based assay termed DSA. We draw the conclusion that due to the unique features and fields of application reviewed here, the implementation of solid phase cross-matching still represents an urgent requirement for any HLA-laboratory's routine tasks.
移植受者在经历致敏事件后，如妊娠、输血或先前的移植，经常会产生针对高度多态性人类白细胞抗原（HLA）分子的抗体。这些预先形成的、针对供体的抗体（DSA）会导致器官衰竭甚至移植器官完全丧失，因为它们会导致抗体介导的超急性或急性同种异体排斥反应。为了检测 DSA，大约 50 年前建立了所谓的功能性补体依赖性细胞毒性测定（CDC-XM）。尽管该测定在改善实体器官同种异体移植的结果方面非常有效，但在过去十年中，由于其敏感性低，特别是由于其对各种人为因素的高度敏感性，该测定一直存在争议，这些因素通常无法产生可靠的结果。因此，已经开发了使用 ELISA 或基于珠的固相测定法替代传统的 CDC 测定法的新型免疫化学测试系统。由于这些测定法不依赖于经常不可用的单个或有活力的细胞，因此与传统的基于 CDC 的和流式细胞术分析相比，提供了额外的替代诊断方法。不幸的是，然而，第一个商业化的 AMS-ELISA（抗体监测系统）在成功使用七年后，制造商最近停止了生产。替代程序，如 AbCross-ELISA，要么需要进行相当大的修改，要么无法产生可靠的结果，例如基于 Luminex 的 DSA 测定。我们得出结论，由于这里审查的独特特征和应用领域，固相交叉匹配的实施仍然是任何 HLA 实验室常规任务的迫切要求。
