Interaction of leucocyte antibodies with endothelial cells in transfusion‐related acute lung injury

Abstract

Transfusion‐related acute lung injury (TRALI) is a severe pulmonary reaction characterized by pulmonary oedema, breathing distress and consequently hypoxia temporally associated with a blood transfusion event. In antibody‐mediated TRALI, alloantibodies reactive with recipient's neutrophils are mainly considered as responsible for lung injury. These antibodies target either human leucocyte antigens (HLAs) class I or II or human neutrophil antigens (HNAs). Antibody interaction with the cognate antigen is believed to induce neutrophil activation and sequestration, which consequently leads to endothelial damage and lung injury. Analysing the effects of these antibodies on neutrophil‐depleted animals however has challenged this dogma. Previous studies have documented that among anti‐HNA antibodies, anti‐HNA‐3a are implicated in severe and fatal TRALI. Epitopes for anti‐HNA‐3 antibodies reside on choline transporter‐like protein 2 (CTL2) which has a broad expression pattern on different cells including neutrophils and endothelial cells. In vitro as well as in vivo research has identified the binding of anti‐HNA‐3a to endothelial cells as initiator of lung injury in anti‐HNA‐3a‐mediated TRALI. Studies have also demonstrated that binding of HLA antibodies to cognate antigens expressed on endothelial cells, by triggering multiple signalling pathways, influences endothelial functions. This presentation will summarize findings on the effects of HNA and HLA antibodies binding to endothelial cells and highlight the contribution of endothelial‐reactive antibodies in the mechanism of antibody‐mediated TRALI.