LAUSR

A ntibody screening during pretransfusion testing is critical to avoid transfusion of incompatible blood and subsequent acute or delayed hemolytic transfusion reactions. Alloantibody identification currently relies on reagent red blood cells obtained from group O donors. For most patients, the combinations of red cell antigen phenotypes readily available from donorderived cells are sufficient to determine antibody specificity. However, for individuals with uncommon phenotypes, particularly those who lack a high prevalence antigen to which they have become immunized, antibody identification is hampered by the paucity of reagent red cells with uncommon phenotypes. Red cells with rare antigen phenotypes are curated and stored frozen by reference laboratories and represent a finite resource that relies on individual blood donations. Thus, alternative sources of reagent red cells with uncommon phenotypes are needed. Erythroid cell lines and induced pluripotent stem cells (iPSCs) are attractive alternatives because they are renewable cell sources and can be genetically engineered to express combinations of blood group antigens that are very rare or never found in humans. In this issue of TRANSFUSION, Kikuchi and colleagues report the use of an immortalized human erythroid progenitor cell line to produce reagent red cells for antibody screening and identification. Specifically, they use HiDEP-1 (human iPSC-derived erythroid progenitor) cells that are immortalized but can undergo maturation when cultured in medium that specifically supports erythroid differentiation. They demonstrate that these in vitro–derived red cells express some red cell antigens (D, C, e, k, Di) at sufficient density to be used in hemagglutination assays. However, their reactivity with monoclonal antibodies directed at antigens within the MNS, Jk, and Fy systems was weak. In the future, this may be addressed by overexpression of exogenous antigens, as lentiviral transduction of HiDEP-1 cells with a Di transgene yielded antigen expression equivalent to endogenous expression of Di. Coupled with gene-editing techniques, in vitro–derived red cells have the potential to enhance blood bank tools to detect and identify rare antibody specificities, resolve fine specificities, and, importantly, alleviate demand for reagent red cells from rare donor units so these can be saved for transfusion.