Thesis Saskia van der Velden

Abstract

The immune system plays a vital role in maintaining homeostasis by balancing pro- and anti-inflammatory responses. Disruptions, such as through blood transfusions, can trigger adverse effects, including Transfusion- Related Acute Lung Injury ( TRALI ), a leading cause of transfusion-related mortality. TRALI manifests within six hours of transfusion, primarily through pulmonary edema and acute respiratory distress, with no specific treatments currently available. It follows a "2-hit model": an underlying condition primes the body (first hit), and transfusion-related antibodies (second hit) trigger the immune reaction.
Chapters 2–6 explore immune cells’ roles in TRALI , particularly platelets, macrophages, eosinophils, and neutrophils (PMNs). Platelets, while mostly known for clotting, also have immune functions. However, their involvement in TRALI appears minimal. Macrophages, particularly when activated by complement component C5a, are key drivers of lung damage in TRALI , and complement inhibition shows therapeutic promise. Eosinophils may regulate macrophage migration via IL-4, and their depletion doesn’t affect TRALI severity, but may influence PMN recruitment. Neutrophils are central to TRALI , with IL-5 and eosinophils modulating their recruitment.
Chapter 7 questions extra-pulmonary involvement, finding no pancreatic damage in contrast to earlier claims. Chapter 8 reflects on the need for more preventive and predictive research, emphasizing understanding disease resolution mechanisms alongside treatment development.
Overall, this body of research deepens understanding of TRALI ’s complex immunopathology and identifies complement activation as a critical pathway, suggesting it as a potential therapeutic target. Continued investigation into immune cell interactions and early biomarkers is essential for improving TRALI prevention and treatment strategies.