Abstract 19


Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated fatalities in developed countries. It has been demonstrated that antibodies to human neutrophil antigens (HNA) present in a blood product can precipitate a TRALI reaction in the blood recipient. In the majority of TRALI cases, however, HLA class II antibodies rather than HNA antibodies are detected in the implicated donor. HLA class II antigens are not present on neutrophils or endothelial cells, the cellular key players in TRALI pathophysiology. Whether or not HLA class II antibodies are capable of inducing TRALI is thus under discussion. Here, we investigated a possible mechanism of HLA class II antibody-induced TRALI via monocytes. Methods and Results: Plasma from blood donors containing HLA class II antibodies (H2+plasma) is capable of activating monocytes expressing cognate antigen(s) as demonstrated by the release of IL-8, GRO-alpha, and TNF-alpha in culture supernatants. H2+plasma does not activate monocytes that do not express the cognate HLA class II antigen(s). Culture supernatants from matched pairs, but not H2+plasma itself, induce a respiratory burst reaction in neutrophils. In Boyden chamber experiments, FITC-albumin transendothelial flux is significantly increased in the presence of H2+plasma, matched monocytes, and neutrophils, but unchanged in the presence of non-matched monocytes. Diphenyleneiodonium chloride inhibits this barrier breakdown. In the ex vivo rat lung model, supernatants from matched pairs, but not from non-matched pairs, are capable of inducing TRALI in the presence, but not in the absence, of neutrophils. H2+plasma precipitates a TRALI in this model if neutrophils and matched, but not non-matched, monocytes are present. IgG-depletion of H2+plasma abolishes this effect. Conclusions: HLA class II antibodies present in donor plasma can induce TRALI in a transfusion recipient via monocyte activation. Once activated, monocytes stimulate neutrophils to produce reactive oxygen species, which lead to an increase in endothelial permeability and subsequent lung edema. This cascade depends on a match between the donor's antibodies and the recipient's HLA class II antigens and can be reproduced in a rat lung model. Our findings have important impact on current strategies that aim to prevent TRALI by donor testing and/or exclusion.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.