Autoantibodies in the serum of donors: Can TRALI be expected?

Transfusion-related acute lung injury (TRALI) is a serious clinical condition characterized by acute non-cardiogenic pulmonary edema that occurs during or after transfusion. Despite numerous prevention strategies, transfusion-related acute lung injury remains a major cause of transfusion-related mortality. The presence of alloantibodies in donor serum is thought to be responsible for 85% of TRALI cases. If TRALI is considered clinically, identified donors are tested for the presence of alloantibodies against human neutrophil- and human lymphocyte antigens (HNA, HLA). Interestingly, the relevance of autoantibodies for the mechanism of TRALI has not been investigated systematically so far.

Eligible cases of suspected TRALI referred to us between 2022 and 2023 were evaluated. All cases in which alloreactivity was excluded, but the donor's serum was reactive in the granulocyte immunofluorescence test, were further analyzed by extended serology and genotyping. CellRox green flow cytometry assay was used to address the question of whether such antibodies can activate neutrophils and lead to the production of reactive oxygen species (ROS).

Between 2022 and 2023, 16 TRALI cases were reported. In this cohort, 41 donors were negative in GIFT. No donors with alloantibodies were detected in the GIFT-positive sera (45 in total). However, 4 sera showed a serological pattern that could indicate the presence of neutrophil autoantibodies. Preliminary analysis of 4 sera from donors with neutrophil autoantibodies, 2 serums with HNA alloantibodies (anti-HNA-2), and negative sera in the CellRox green flow cytometry assay showed that both sera with autoantibodies and alloantibodies were able to induce neutrophil ROS production. However, this effect was more pronounced with alloantibodies (p<0.05).

Due to the male-only plasma strategy, no donor with allo-reactivity was detected in this cohort. However, donors with autoantibodies were involved in suspected cases of TRALI. In vitro analysis indicates that the binding of these autoantibodies to neutrophils triggers ROS production. Further analysis is required to decipher the TRALI-inducing potential of these antibodies.

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