Grant: Operating Grant - PA: Transfusion Related Acute Lung Injury (TRALI)

Transfusion-related acute lung injury (TRALI) denotes lung injury soon after a patient receives a blood transfusion and currently, there is no therapy for this transfusion complication. With a death rate of 5-14%, TRALI has recently been ranked as the leading cause of transfusion-related death; recent clinical studies have also suggested that approximately 3-5% of all deaths in cardiac surgery patients are due to TRALI-like lung complications. The mechanisms of how TRALI occurs are not completely clear, but host immunity together with substances within the blood product is thought to be the main factors involved. It appears that the majority (approximately 85%) of cases of TRALI involve the transfusion of antibodies that react with cells within the patient's lungs. This interaction causes the cells to become activated and release substances that damage the lung tissue. Perhaps more intriguing is that many units that cause TRALI in one recipient do not cause lung injury in others indicating that recipient factors may also be in play. We have developed a mouse model of antibody-mediated TRALI to study these recipient factors and have found that a recipient lymphocyte termed a CD8+ T cell is responsible for dampening lung injury (Fung et al Blood, 2010). We have used this result and others to design experimentation and tests to determine the exact role that recipient immune factors play in initiating or modulating TRALI reactions. Understanding these factors may lead to the identification of recipients at risk of developing TRALI and lead to novel therapies for the treatment of TRALI.