Fienberg School of Medicine, Department of Surgery, Comprehensive Transplant Center, Northwestern University, Chicago, Illinois, USA.
Division of Nephrology & Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
HLA. 2022 Nov;100(5):457-468. doi: 10.1111/tan.14781. Epub 2022 Aug 29.
Luminex single antigen bead (SAB) testing has increased the sensitivity and specificity of accurately identifying HLA antibodies, in support of all organ transplantation. However, as described in manufacturers' recommendation, the output of the assay, using mean fluorescence intensity (MFI) units, is only semi-quantitative. Therefore, the ability to use MFI values to compare between different assays, to accurately guide clinical practice, or be used as an endpoint measure in clinical trials, is limited. To improve potential quantification, one must circumvent inherent limitations of SAB assays such as interference and saturation phenomena. In this review, we discuss how measurement of pre-transplant serum dilutions can be used to determine unacceptable antigens for wait-listing, determine the likelihood for successful HLA antibody reduction with desensitization, and compare degree of HLA (in)compatibility among various living donors. We also discuss how serum dilutions are optimal for measuring and comparing the efficacy of antibody depletion therapies for desensitization or antibody mediated rejection treatment post-transplant. Historically, one of the main criticisms for the use of serum dilutions and titer has been the potential labor and cost associated with additional testing. Here, we show how only one or two dilutions can add major value in most circumstances. In summary, the practical use of serum dilutions and titer determination are important methods that can be used before and after transplantation of all organs to quantify antibody accurately and reliably in routine practice and in clinical trials.
Luminex 单抗原珠 (SAB) 检测提高了准确识别 HLA 抗体的灵敏度和特异性，支持所有器官移植。然而，正如制造商建议中所描述的，该检测的输出结果（使用平均荧光强度 (MFI) 单位）仅为半定量。因此，使用 MFI 值来比较不同检测之间的能力，准确指导临床实践，或作为临床试验的终点测量，是有限的。为了提高潜在的定量能力，必须规避 SAB 检测固有的限制，如干扰和饱和现象。在这篇综述中，我们讨论了如何使用移植前血清稀释液来确定等待名单上不可接受的抗原，确定脱敏治疗成功降低 HLA 抗体的可能性，以及比较不同活体供者之间 HLA（不）相容性的程度。我们还讨论了血清稀释液如何最适合测量和比较脱敏或移植后抗体介导排斥治疗中抗体耗竭疗法的疗效。历史上，使用血清稀释液和滴度的主要批评之一是与额外检测相关的潜在劳动力和成本。在这里，我们展示了在大多数情况下，仅使用一个或两个稀释度就可以增加主要价值。总之，在所有器官移植前后，血清稀释液和滴度的实际使用是一种重要的方法，可以在常规实践和临床试验中准确可靠地定量抗体。
