Mechanism of pulmonary endothelial cell damage in reverse TRALI due to transfused sCD177/PR3 and recipient CD177-antibodies

• Applicant: Dr. Behnaz Bayat
• Subject Area: Pneumology, Thoracic Surgery ; Immunology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568537503

Blood transfusions are frequently administered in diverse clinical settings and are often life-saving. Unfortunately, and unexpectedly, life-threatening adverse transfusion reactions may also occur. This includes Transfusion-related acute lung injury (TRALI) which is characterized by damage to the pulmonary endothelium resulting in pulmonary edema and acute respiratory distress, and which remains a leading cause of blood transfusion-related mortality (Semple et al, Blood 2019). TRALI occurs within 6 hours of a blood transfusion and currently there are no specific treatments available (Vlaar et al, Transfusion 2019; Semple et al, Crit Care Med 2018). The pathophysiology has proven to be complex. A two-hit principle is postulated to underlie TRALI, where the first hit is conveyed by the underlying clinical condition of the patient, while the second hit is conveyed by factors present in the blood transfusion product (Semple et al, Blood 2019, Silliman et al, J Clin Invest 1998; Silliman, Crit Care Med 2006; Silliman et al, Blood 2007). In “classic TRALI”, factors in the transfusion product may include leukocyte/endothelial-reactive antibodies or biological response modifiers such as lipids. Recently, however, clinical awareness and the urge for understanding the pathophysiology has increased for so-called “reverse TRALI”, in which antibodies present in the recipient damage the pulmonary endothelium upon a blood transfusion (Basu et al, Transfus Apher Sci 2022; Bayat et al, Blood Adv 2021; Jug et al, Transfusion 2021; De Clippel et al, Transfusion 2019). How this exactly occurs on a mechanistic level remains to be elucidated. This proposal will focus on further investigating the mechanism of reverse TRALI based on transfused sCD177/PR3 and recipient CD177-antibodies, using both in vitro and in vivo approaches, which may ultimately be exploited to combat the mortality due to blood transfusions.

• DFG Programme: Research Grants