Neutrophil-reactive autoantibodies in blood donors: Can we expect TRALI?

Transfusion-related acute lung injury (TRALI) is a clinical condition characterized by acute non-cardiogenic pulmonary edema during or after transfusion. Despite several mitigation strategies, TRALI remains a leading cause of transfusion-related deaths. Tests on blood donors involved in TRALI, apart from leukocyte/endothelial reactive alloantibodies, can also reveal the presence of neutrophil autoantibodies. Here, we ask the question whether these autoantibodies could play a role in the development of TRALI.

Sera (n = 15) from donors involved in TRALI and not containing alloantibodies against human neutrophil antigens (HNAs) and human leukocyte antigens (HLAs) were collected if their serological characterization was suggestive for the presence of neutrophil-reactive autoantibodies. Sera (n = 12) were suitable for the study. Their ability to bind complement, to activate neutrophils, and to disrupt the endothelial barrier using albumin influx through an endothelial monolayer in a transwell chamber in the presence and absence of neutrophils was investigated.

None of the AIN sera, but 2/12 TRALI sera, induced reactive oxygen species (ROS) in neutrophils. Both of these TRALI sera induced endothelial barrier permeability in the presence, but not in the absence, of neutrophils. These two sera did not activate complement.

Autoantibodies against neutrophils present in transfused blood components appear to be capable of contributing to TRALI in selected but not in all investigated cases, based on their ability to activate neutrophil ROS and induce endothelial cell permeability in vitro. Further analysis is required to understand the potential functional effects of neutrophil autoantibodies in TRALI.