Jürgen Bux

The pathogenesis of transfusion-related acute lung injury (TRALI).

In recent years, transfusion‐related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion‐related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non‐cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patients co‐morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

Specificities of leucocyte alloantibodies in transfusion-related acute lung injury and results of leucocyte antibody screening of blood donors

Background  Antibody‐mediated transfusion‐related acute lung injury (TRALI) is an important cause of transfusion‐associated morbidity and death. Preventive strategies are currently a matter of debate.

Transfusion-related acute lung injury due to HLA-A2-specific antibodies in recipient and NB1-specific antibodies in donor blood.

Transfusion‐related acute lung injury (TRALI) is a hazardous but little‐known complication of blood transfusion, characterized by non‐cardiogenic lung oedema after blood transfusion. Leucoagglutinating antibodies in the donor plasma are considered to play a central role in the pathogenesis of TRALI but no recommended procedure currently exists for their detection, and most of them have not yet been well characterized. Serum samples of two patients who have developed TRALI within 30 min of blood transfusion and the sera of the involved blood donors were investigated for leucocyte antibodies by granulocyte immunofluorescence, granulocyte agglutination and lymphocytotoxicity assays using typed test cells. Suspected specificities of the detected antibodies were confirmed by a luminoimmunoblot assay and the antigen capture assay MAIGA. One case was associated with granulocyte agglutinating anti‐HLA‐A2 antibodies in the recipient’s (i.e. patients) own blood and the other with donor‐related non‐agglutinating antibodies directed against the granulocyte‐specific antigen NB1. Leucocyte incompatibility between donor and recipient was shown in both cases by crossmatching and typing of the incompatible cells for the appropriate antigen. The results show that TRALI is associated not only with donor‐ but also with recipient‐related leucocyte antibodies. In addition to leucoagglutinating antibodies, non‐agglutinating granulocyte‐specific antibodies can be also involved. For immunodiagnosis, sera from both must be investigated by a combination of granulocyte and lymphocyte (HLA) antibody screening tests and leucocyte incompatibility verified by crossmatching.

TRALI due to granulocyte‐agglutinating human neutrophil antigen‐3a (5b) alloantibodies in donor plasma: a report of 2 fatalities

BACKGROUND : TRALI is usually an immunologic reaction to WBC antibodies in infused plasma and ranks second only to ABO mismatch as a cause of transfusion‐associated death. Implicated donors are usually multiparous women (≥3 pregnancies).

Human neutrophil alloantigens

Objective  This review describes alloantigens currently listed in the human neutrophil alloantigen (HNA) system.

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II-induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody-dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody-induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures.

Recommendations of the ISBT Working Party on Granulocyte Immunobiology for leucocyte antibody screening in the investigation and prevention of antibody-mediated transfusion-related acute lung injury.

Background  Transfusion‐related acute lung injury (TRALI) is currently one of the most common causes of transfusion‐related major morbidity and death. Among the many TRALI mediators, leucocyte antibodies have been identified as important triggers of severe TRALI.

TRALI after the transfusion of cross‐match‐positive granulocytes

BACKGROUND: TRALI is a serious complication of transfusion. WBC antibodies have been associated with TRALI. The importance of such antibodies for the transfusion of granulocytes is unknown.

Antibody‐mediated (immune) transfusion‐related acute lung injury

Antibody‐mediated transfusion‐related acute lung injury (immune TRALI) is now recognized as the most common cause of transfusion‐associated major morbidity and death in the Western world. Among the implicated leucocyte antibodies, these ones directed against the human leucocyte antigens (HLA) class II, human neutrophil alloantigens (HNA)‐3a and HLA‐A2 antigens are frequently associated with severe (artificial ventilation required) and fatal cases. There is accumulating evidence that preventive measures such as transfusion of plasma‐rich blood components from male donors or from donors tested negative for leucocyte antibodies are effective in the reduction of severe and fatal immune TRALI.

Measures to prevent transfusion-related acute lung injury (TRALI)

H. W. Reesink, J. Lee, A. Keller, P. Dennington, J. Pink, R. Holdsworth, H. Schennach, M. Goldman, T. Petraszko, J. Sun, Y. Meng, K. Qian, V. Rehacek, P. Turek, T. Krusius, E. Juvonen, P. Tiberghien, D. Legrand, G. Semana, J. Y. Muller, J. Bux, A. Reil, C. K. Lin, H. Daly, E. McSweeney, L. Porretti, N. Greppi, P. Rebulla, H. Okazaki, S. A. Sanchez-Guerrero, H. A. Baptista-Gonzalez, C. Martinez-Murillo, A. Guerra-Marquez, H. Rodriguez-Moyado, R. A. Middelburg, J. C. Wiersum-Osselton, A. Brand, C. van Tilburg, D. Dinesh, J. Dagger, P. Dunn, E. Brojer, M. Letowska, K. Maslanka, E. Lachert, M. Uhrynowska, E. Zhiburt, M. Palfi, G. Berlin, B. M. Frey, L. Puig Rovira, E. Muniz-Diaz, E. Castro, C. Chapman, A. Green, E. Massey, N. Win, L. Williamson, C. C. Silliman, D. J. Chaffin, D. R. Ambruso, N. Blumberg, P. Tomasulo, K. J. Land, P. J. Norris, O. C. Illoh, R. J. Davey, R. J. Benjamin, A. F. Eder, L. McLaughlin, S. Kleinman & S. Panzer