Using the definition in this report, clinicians can diagnose and report TRALI cases to the blood bank; importantly, researchers can use this definition to determine incidence, pathophysiology, and strategies to prevent this leading cause of transfusion-associated mortality.

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is a serious, sometimes fatal, complication of transfusion. Granulocyte and HLA class I antibodies present in blood donors have been associated with TRALI. HLA class II antibodies have recently been described in a few cases of TRALI. STUDY DESIGN AND METHODS: Donors involved in TRALI reactions reported to a blood center over an 18‐month period were tested for HLA class I and II antibodies as well as granulocyte antibodies, if HLA antibodies were not identified. RESULTS: HLA class II antibodies were identified, in at least one donor, in 7 (64%) of 11 cases of TRALI. HLA class I antibodies were identified in combination with HLA class II antibodies in 5 of these 7 cases. HLA class I antibodies were exclusively identified in 2 cases. Granuloctye antibodies were identified in 1 case, and no antibodies were identified in another. CONCLUSION: In addition to HLA class I antibodies, HLA class II antibodies are associated with TRALI. Testing of donors for HLA class II antibodies as well as HLA class I and granulocyte antibodies is recommended as part of the investigation of suspected cases of TRALI.

In most cases of TRALI, a correlation between antigen and antibody can be identified. Activation of monocytes and their subsequent release of cytokines may play a role in the pathogenesis of TRALI.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. Antibodies to HNA-3a are commonly implicated in TRALI. We hypothesized that HNA-3a antibodies prime neutrophils (PMNs) and cause PMN-mediated cytotoxicity through a two-event pathogenesis. Isolated HNA3a ؉ or HNA-3a ؊ PMNs were incubated with plasma containing HNA-3a antibodies implicated in TRALI, and their ability to prime the oxidase was measured. Human pulmonary microvascular endothelial cells (HMVECs) were activated with endotoxin or buffer, HNA-3a ؉ or HNA-3a ؊ PMNs were added, and the coculture was incubated with plasma ؎ antibodies to HNA-3a. PMN-mediated damage was measured by counting viable HMVECs/mm 2 . Plasma containing HNA-3a antibodies primed the fMLP-activated respiratory burst of HNA-3a ؉ , but not HNA-3a IntroductionTransfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related death in the United States. 1 The pathogenesis of TRALI includes the infusion of specific antibodies from the donor directed against antigens (HLA class I or class II, or granulocyte specific) present on the recipient's leukocytes resulting in complement activation, neutrophil (PMN) sequestration, and activation in the lung, culminating in endothelial damage, capillary leak, and acute lung injury (ALI). [2][3][4][5] An ex vivo lung model confirmed that antibodies against HNA-3a, together with HNA-3a ϩ PMNs, and plasma caused ALI. 6,7 The HNA-3a locus is present in 95% of humans, and antibodies directed against this antigen are one of the most commonly implicated immunoglobulins in TRALI, including 3 reported fatalities and a "look-back" study of 1 donor with HNA-3a antibodies that demonstrated that a number of patients developed TRALI that were not reported; however, TRALI occurred in a minority of patients transfused. 8,9 A two-event pathogenesis for TRALI has also been proposed such that the first event, related to the patient's underlying clinical condition, elicits activation of the pulmonary endothelium causing sequestration of PMNs in the microvasculature. 10 The second event is the infusion of specific antibodies directed against antigens on the granulocyte or biologic response modifiers (BRMs), which activate the microbicidal arsenal of the sequestered PMNs resulting in endothelial damage, capillary leak, and ALI. 10 This model has been confirmed in a rat lung model and in vitro using human pulmonary microvascular endothelial cells (HMVECs) as targets. [11][12][13] We hypothesize that antibodies directed against HNA-3a prime PMNs and cause PMN-mediated cytotoxicity. Patients, materials, and methodsAll chemicals were purchased from Sigma Chemical (St Louis, MO). All solutions were made from sterile water or sterile 0.9% saline for intravenous administration (United States Pharmacopeia [USP], Baxter Healthcare, Deerfield, NY) as reported. 10 Antibodies to CD18 or to intercellular adhesion molecule-1 (ICAM-1) were purchased from PharMingen (Torrey Pines, CA) and Ancell (Bayport, MN), r...