Spotlight on pathogenesis of TRALI: HNA-3a (CTL2) antibodies

Human neutrophil antigen-3a (HNA-3a) antibodies contained in donor plasma can result in severe, sometimes fatal transfusion-related acute lung injury (TRALI). Recent developments in TRALI secondary to antibodies to HNA-3a antigen span diagnosis, pathophysiology, treatment, and prevention resulting in improved understanding, potential treatments, and mitigation strategies. First, on the molecular level, characterization of HNA-3 antigen has allowed for genotyping methods that clarify population prevalence. Related work has led to generation of multiple antibody detection assays. These assays aid in determining potential populations at risk and potential mitigation strategies. Second, the development of TRALI requires a hit from the patient and from the product. Anti-HNA-3a is one of the product-derived factors and appears to result in TRALI by binding directly to pulmonary endothelium as well as to neutrophils expressing the corresponding antigen. Finally, potential mitigation strategies include red blood cell product filtration to remove anti-HNA-3a as well as other antibodies.