Pulmonary transfusion reactions as an immunological spectrum disorder

Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are leading causes of transfusion-related morbidity and mortality. Despite distinct diagnostic criteria, both syndromes present similarly with respiratory distress and pulmonary edema. In recent research, they increasingly appear to share pathophysiological and immunological features. In this review, we discuss current evidence supporting a spectrum model of pulmonary transfusion reactions, spanning hydrostatic to permeability edema. We highlight key immunological mechanisms in TRALI, including Fc-receptor or complement engagement, and cytokine responses, and explore emerging evidence of immune involvement in TACO. To differentiate, the anti-inflammatory cytokine interleukin (IL)-10 and pro-inflammatory IL-6 emerge as potential biomarkers with diagnostic and therapeutic implications. The underdiagnosis of reverse TRALI and TRALI/TACO overlap further highlights the need for additional mechanistic insight and improved diagnostics. Future work should focus on biomarker-guided phenotyping to improve clinical differentiation and treatment strategies for transfusion-related respiratory complications as a spectrum disorder.