Department of Pathology and Laboratory Medicine, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Hum Immunol. 2020 Feb-Mar;81(2-3):65-72. doi: 10.1016/j.humimm.2020.01.007. Epub 2020 Feb 10.
Virtual crossmatch (VXM) compares a transplant candidate's unacceptable antigens to the HLA typing of the donor before an organ offer is accepted and, in selected cases, supplant a prospective physical crossmatch. However, deceased donor typing can be ambiguous, leading to uncertainty in compatibility prediction. We have developed a prototype web application that utilizes ambiguous HLA molecular typing data to predict which unacceptable antigens are present in the donor HLA genotype as donor-specific antibodies (DSA). The application compares a candidate's listed unacceptable antigens to computed probabilities of all possible two-field donor HLA alleles and UNOS antigens. The VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) tool can be accessed at http://www.transplanttoolbox.org/victor. We reanalyzed historical VXM cases where a transplant center's manual interpretation of molecular typing results influenced offer evaluation. We found that interpretation of ambiguous donor molecular typing data using imputation could one day influence VXM decisions if the DSA predictions were rigorously validated. Standardized interpretation of molecular typing data, if applied to the match run, could also change which offers are made. HLA typing ambiguity has been an underappreciated source of immunological risk in organ transplantation. The VICTOR tool can serve as a testbed for development of allocation policies with the aim of decreasing offers refused due to HLA incompatibility.
虚拟交叉配型 (VXM) 在接受器官捐献之前，将移植候选者的不可接受抗原与供体的 HLA 类型进行比较，并在选定情况下替代预期的物理交叉配型。然而，已故供体的类型可能存在歧义，导致对相容性预测的不确定性。我们开发了一个原型网络应用程序，该程序利用 HLA 分子类型的不明确数据来预测供体 HLA 基因型中存在哪些不可接受的抗原作为供体特异性抗体 (DSA)。该应用程序将候选者列出的不可接受的抗原与计算的所有可能的两个字段供体 HLA 等位基因和 UNOS 抗原的概率进行比较。可以在 http://www.transplanttoolbox.org/victor 访问 VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) 工具。我们重新分析了历史上的 VXM 案例，其中移植中心对手动解释分子类型结果影响了评估。我们发现，如果对 DSA 预测进行严格验证，使用推断解释不明确的供体分子类型数据有朝一日可能会影响 VXM 决策。如果将分子类型数据的标准化解释应用于匹配运行，也可能会改变提供的器官。HLA 类型的不明确性一直是器官移植中免疫风险的一个被低估的来源。VICTOR 工具可以作为开发分配政策的试验台，目的是减少因 HLA 不兼容而拒绝的器官捐献。
