The Significance and Prospects of Introducing the Japanese Virtual Crossmatch System in Organ Transplantation.

Abstract

Crossmatch testing is a critical step in organ transplantation, used to evaluate donor–recipient compatibility and predict the risk of antibody-mediated rejection. Conventional physical crossmatch (PXM) assays, such as complement-dependent cytotoxicity and flow cytometric methods, face major logistical and temporal limitations, including specimen transport and round-the-clock testing demands. Virtual crossmatch (VXM), which compares donor HLA typing data with recipient anti-HLA antibody profiles in silico, has emerged as a promising alternative. Based on the single antigen bead (SAB) assay, VXM allows simultaneous quantification of numerous HLA-specific antibodies and can accurately predict PXM results without using donor cells. VXM has already been implemented in the United States, United Kingdom, Eurotransplant countries, Australia, and New Zealand, improving allocation efficiency and reducing ischemia time. In Japan, an interdisciplinary committee was established in 2023 to promote VXM adoption, and by 2025, the national policy allowing omission of PXM in antibody-negative cases was officially approved. Future challenges include integration of antibody data into a unified registry, refinement of algorithms to compensate for SAB assay limitations, incorporation of AI-based predictive modeling, and standardization of donor HLA typing using next-generation sequencing. Despite remaining technical issues, VXM represents a transformative approach to achieving safer, faster, and more equitable organ transplantation.