Recent advances in laboratory assays for nonhemolytic transfusion reactions

Nonhemolytic transfusion reactions (NHTRs) are the most common transfusion reactions and include transfusion-related acute lung injury (TRALI) and allergic and febrile reactions. White blood cell (WBC) antibodies (Abs) against human leukocyte antigen (HLA) and human neutrophil antigen (HNA) in blood components are frequently implicated in NHTRs, especially in TRALI. Recently, we established a five-cell-lineage immunofluorescence test, a modified granulocyte immunofluorescence test, and a panel of cell lines stably expressing HNAs for efficient detection of Abs against well-known HNA-1 to HNA-5, and also Abs against neutrophil antigens other than HNA-1 to HNA-5. Using these techniques, we found that most of the non-HLA WBC Abs detected in NHTR cases were against antigens other than HNA-1 to HNA-5. In addition, using our newly established neutrophil activation test, which assesses neutrophil activation elicited by immunologic stimuli such as WBC Abs and immune complex, we found that heparin-binding protein is a potential final effector molecule that induces NHTRs, including TRALI. More recently, we reported that the basophil activation test, which was originally developed to identify allergens in the field of allergic diseases, might be useful in transfusion medicine. In this review, we summarize these new techniques and other related tests.