Virtual and Reality: An Analysis of the UCLA Virtual Crossmatch Exchanges

The "virtual" crossmatch (VXM) has become a critical tool to predict the compatibility between an organ donor and a potential recipient. Yet, nonstandardized laboratory practice can lead to variability in VXM interpretation. Therefore, UCLA's VXM Exchange survey was designed to understand factors that influence the variability of VXM prediction in the presence of HLA donor-specific antibody (DSA). Thirty-six donor blood samples and 72 HLA reference sera were sent to 35 participating laboratories to perform HLA antibody testing, flow crossmatch (FXM), and VXM from 2014 to 2019, consisting of 144 T/B-cell FXM pairs and 112 T/B-cell VXM pairs. In the FXM survey, 86% T-cell FXM and 84% B-cell FXM achieved >80% concordance among laboratories. In the VXM survey, 81% T-cell VXM and 80% VXM achieved >80% concordance. The concordance between FXM and VXM was 79% for T cell and 87% for B cell. The consensus between VXM and FXM was high with strong DSA. However, significant variability was observed in sera with (1) very high titer antibodies that exit prozone effect; (2) weak-to-moderate DSA, particularly in the presence of multiple weak DSAs; and (3) DSA against lowly expressed antigens. With the increasing use the VXM, standardization and continuous learning via exchange surveys will provide better understanding and quality controls for VXM to improve accuracy across all centers.