Utilizing proficiency testing survey data to create advanced educational content: the virtual crossmatch challenge model

Proficiency testing (PT) surveys include data from laboratories across the world and are ideal for creating advanced educational content, beyond just consensus grading. Educational challenges provide a unique opportunity to probe common laboratory practices and risk assessment, especially in cases where there is no "analyte" tested. Human leukocyte antigen (HLA) compatibility evaluation between donor and recipient pairs has been traditionally assessed using T-cell and B-cell physical crossmatches. However, advancements in our ability to identify and characterize HLA antibodies using solid phase assays, in combination with changing deceased donor allocation schemes and improved HLA typing, have shifted the paradigm from performing physical crossmatches to the use of the virtual crossmatch (VXM). VXM is a compatibility assessment relying on the interpretation of pre-transplant HLA laboratory data and as such, it is not an "analyte". However, VXM results are used in clinical decision-making. The VXM assessment depends on patient characteristics as well as laboratory and transplant center practices but must ensure safe transplantation outcomes while maintaining equity in access to transplantation. In this manuscript, we describe the American Society for Histocompatibility and Immunogenetics (ASHI) PT Educational VXM Challenge, as a model for creating educational content using PT survey data. We discuss the different components of the VXM Challenge and highlight major findings and learning points acquired from ASHI VXM Challenges performed between 2018-2022, such as the lack of correlation between the VXM and the physical crossmatch in the presence of low level donor-specific antibodies (DSA), or when the DSA were aimed against donor alleles that are not present on the antibody panel, and in the presence of an antibody to a shared eplet. Finally, we show that the VXM Educational Challenge serves as a valuable tool to highlight the strengths and pitfalls of the VXM assessment and reveals differences in testing and result interpretation among participating HLA laboratories.