Transfusion of Target Antigens to Pre-Immunized Recipients: A New Mechanism in Transfusion-Related Acute Lung Injury

Behnaz Bayat, Kaspar Rene Nielsen, Gregor Bein, Annalena Traum, Monika Burg-Roderfeld, Ulrich J Sachs

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

7 Citationer (Scopus)
17 Downloads (Pure)

Abstract

Transfusion-related lung injury (TRALI) is a serious side effect of blood transfusion. Exclusion of antibody carriers from the donor pool has significantly decreased the number of cases, but TRALI remains the leading cause of transfusion-related morbidity and mortality in industrialized countries. Here, we show that proteins released from donor cells during processing of blood components are capable of inducing a new type of reverse TRALI when transfused to preimmunized recipients. First, we show that soluble neutrophil surface protein CD177 in complex with proteinase 3 (sCD177/PR3) is not only present in human plasma but also in packed red blood cell (PRBC) supernatant. Filtration or storage enhances the concentration of sCD177/PR3 in PRBCs. Second, we show that sCD177/PR3 specifically binds to PECAM-1 on stimulated (but not on unstimulated) endothelial cells (ECs). Third, we provide evidence that the sCD177/PR3/PECAM-1 complex is functional. In the presence of monoclonal or human antibodies against CD177 or PR3, ECs produce reactive oxygen species and become apoptotic. Albumin flux through an EC monolayer increases significantly whenever antibodies and the cognate antigens are present. Finally, we describe a clinical case in which anti-CD177 present in a transfusion recipient precipitated TRALI after the transfusion of CD177-positive, but not CD177-negative, PRBCs. In conclusion, we introduce a new TRALI mechanism based on the specific binding of transfused, soluble antigens to activated ECs in preimmunized recipients. We suggest that further studies and clinical work-up of TRALI should also include antibody investigation of the recipient.

OriginalsprogEngelsk
TidsskriftBlood advances
Vol/bind5
Udgave nummer20
Sider (fra-til)3975-3985
Antal sider11
ISSN2473-9529
DOI
StatusUdgivet - 26 okt. 2021

Bibliografisk note

© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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