This is an STTR Phase I application to fund proof of concept studies for a sensitive, accurate, and fully-automated blood screening assay to detect antibodies implicated in TRALI (Transfusion Related Acute Lung Injury). TRALI has become the leading cause of post-transfusion mortality in industrialized countries. Current evidence suggests that many (if not the majority) of TRALI cases are due to antibodies in the donated blood component that bind to allogeneic HLA class I and class II antigens, as well as human neutrophil antigens (HNA), on leukocytes of the recipient. Activated and/or agglutinated recipient leukocytes then lodge in the small capillaries of the lung, leading to severe pulmonary edema and hypoxemia. Because treatment is largely supportive (including intubation and mechanical ventilation), and mortality rates of 6-10% or higher have been reported, preventative strategies are needed. In this application, we provide proof of concept for an accurate and automated screening assay for TRALI antibodies: anti-HLA class I antibodies in patient plasma can be detected with excellent sensitivity and specificity using human HLA class I-coated beads and a fully-automated blood bank multianalyzer (3Ti-Aegis). This workstation, developed through previous STTR support, has already been shown to perform rapid, accurate, and cost- effective blood typing with walk-away automation. The present study will add to the roster of tests available on this instrument, and will demonstrate that testing for antibodies implicated in TRALI is possible with throughput compatible with blood center screening. The Specific Aims of this Phase I application are: (1) To develop and optimize a multi-specificity bead cocktail for simultaneous detection of antibodies against HLA class-I, class-II, and neutrophil (e.g., HNA-1abc, HNA-4a) antigens; and (2) To perform an in-house clinical trial comparing test sensitivity and accuracy with externally performed manual assays. Successful completion of this work will support a Phase II application, with the goals of performing multicenter clinical trials with the assay leading to FDA 510(k) approval. Implications and relevance to public health: While blood transfusions are life-saving interventions, they can be complicated by side effects. One potentially lethal adverse effect is TRALI, in which antibodies in the blood donor can produce lung injuries in the transfusion recipient. This application proposes to develop a test that could be used to screen blood donors for these antibodies, thus preventing TRALI and improving patient outcomes.
Thesaurus Terms: antibody titering, blood group incompatibility, blood transfusion, high throughput technology, histocompatibility antigen, histocompatibility typing, immunohematology, lung injury, method development, neutrophil blood donor, evaluation /testing, leukocyte antigen typing, therapy adverse effect biotechnology, human tissue, immunomagnetic separation
