The virtual crossmatch--a screening tool for sensitized pediatric heart transplant recipients

Heart transplantation in the setting of human leukocyte antigen (HLA) sensitization is challenging, as a time-consuming prospective crossmatch (XM) may be required, severely limiting the number of potential donors. We evaluated a 'virtual XM', defining a positive virtual XM as the presence of recipient pre-formed anti-HLA antibodies to the prospective donor HLA type, and compared the virtual XM to a standard direct XM. Bead-based flow cytometric analysis was used to identify anti-HLA antibody (Ab) present in a child listed for heart transplantation. Using recipient serum, direct-flow cytometric T- and B-cell XM were run for potential donors against whose HLA type the recipient had specific antibodies (group 1, n = 7) and for potential donors with predicted compatible HLA types by virtual XM (group 2, n = 7). Results were expressed as median channel difference (MCD) between the control and recipient serum. A positive T-cell XM was defined as MCD > 50, whereas MCD > 100 constituted a positive B-cell result. The rate of T-cell reactivity was significantly less in group 2 than in group 1 (29% vs. 100%, p = 0.02); similarly, B-cell reactivity was also less for group 2 (14% vs. 100%, p = 0.005). The virtual XM was 100% sensitive in detecting positive flow cytometric XM results for T and B cells. Although only 72% specific in predicting a negative T-cell XM, and 86% specific for negative B-cell XM, the false negatives were weakly positive and would probably have been clinically acceptable. Currently, potentially suitable donor organs are often declined for lack of a prospective XM; these organs may ultimately be allocated to more distant recipients or perhaps not used at all. While further studies are needed, virtual XM has the potential to improve availability of organs for sensitized patients and improve the overall allocation process.