HLA class II antibodies in transfusion‐related acute lung injury

Kopko, Patricia; Popovsky, Mark; MacKenzie, Malcolm R.; Paglieroni, Teresa; Muto, Kathryn N.; Holland, Paul V.

doi:10.1046/j.1537-2995.2001.41101244.x

Cited by 211 publications

(189 citation statements)

References 35 publications

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“…In 2001, antibodies to HLA class II were reported to be associated with TRALI in a series of 11 patients (Kopko et al, 2001). In this study, HLA class II antibodies were detected in combination with HLA class I antibodies in five cases, and as the only entity in two cases.…”

Section: Antibodies To Human Leucocyte Antigenssupporting

confidence: 48%

The pathogenesis of transfusion‐related acute lung injury (TRALI)

2007

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SummaryIn recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, noncardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

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Section: Antibodies To Human Leucocyte Antigenssupporting

confidence: 48%

The pathogenesis of transfusion‐related acute lung injury (TRALI)

2007

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“…In the 3 experimental filters (B, P, and M), there is only an increase in priming activity in the RBC supernatants on day 42 vs day 1 (*P , .05 vs day 1 supernatant). The priming activity from supernatants from RBC units that underwent standard LR was significant from the experimental filtration groups on both day 21 For personal use only. on April 27, 2019. by guest www.bloodjournal.org From filtration with removal of antibodies, leukocytes, and sCD40L may make transfusions safer with diminution of the proinflammatory activity of RBC units.…”

Section: Discussionmentioning

confidence: 99%

“…TRALI in a susceptible host has been related to the infusion of donor antibodies against the HLA antigens of the recipient, which may reside on either the recipient's leukocytes or endothelial cells, or the infusion of lipids or sCD40L. [21][22][23] These antibodies, lipids, or sCD40L activate neutrophils (PMNs), allowing for PMN-mediated endothelial damage, capillary leak, and acute lung injury (ALI). [6][7][8]13,24 We hypothesize that a prestorage filter that removes antibodies, leukocytes, and platelets and decreases lipid bioactivity would significantly decrease the presence of donor HLA antibodies and the accumulation of biologically active lipids and sCD40L and would abrogate TRALI in a 2-event animal model.…”

Section: Introductionmentioning

confidence: 99%

Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo

Silliman

Kelher

Khan³

et al. 2014

Blood

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Key Points• TRALI may be induced by antibodies to HLA or HNA antigens or lipids, which accumulate during storage.• Prestorage experimental filtration of RBCs removes HLA and HNA antibodies, decreases lipid priming activity, and mitigates TRALI in an animal model.Transfusion-related acute lung injury (TRALI) remains a significant cause of transfusionrelated mortality with red cell transfusion. We hypothesize that prestorage filtration may reduce proinflammatory activity in the red blood cell (RBC) supernatant and prevent TRALI. Filters were manufactured for both small volumes and RBC units. Plasma containing antibodies to human lymphocyte antigen (HLA)-A2 or human neutrophil antigen (HNA)-3a was filtered, and immunoglobulins and specific HNA-3a and HLA-2a neutrophil (PMN) priming activity were measured. Antibodies to OX27 were added to plasma, and filtration was evaluated in a 2-event animal model of TRALI. RBC units from 31 donors known to have antibodies against HLA antigens and from 16 antibody-negative controls were filtered. Furthermore, 4 RBC units were drawn and underwent standard leukoreduction. Immunoglobulins, HLA antibodies, PMN priming activity, and the ability to induce TRALI in an animal model were measured. Small-volume filtration of plasma removed >96% of IgG, antibodies to HLA-A2 and HNA-3a, and their respective priming activity, as well as mitigating antibodymediated in vivo TRALI. In RBC units, experimental filtration removed antibodies to HLA antigens and inhibited the accumulation of lipid priming activity and lipid-mediated TRALI. We conclude that filtration removes proinflammatory activity and the ability to induce TRALI from RBCs and may represent a TRALI mitigation step. (Blood. 2014;123(22):3488-3495)

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“…4,13 Antibodies that have been implicated in TRALI include donor HLA class I, HLA class II, and/or neutrophil-specific antibodies. 1,4,[11][12][13][14] Although a number of neutrophil-specific antibodies have been reported, the most common is directed at the 5b (HNA3a) antigen. 6,15 In a small percent of cases, the leukoagglutinating antibody appears to be from the recipient and is directed at the transfused neutrophils.…”

Section: Immune (Antibody)-mediated Tralimentioning

confidence: 99%

Transfusion-Related Acute Lung Injury: An Update

Triulzi

2006

Hematology

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Transfusion-associated acute lung injury (TRALI) has emerged as a leading cause of transfusion-related morbidity and mortality. TRALI is characterized by acute non-cardiogenic pulmonary edema and respiratory compromise in the setting of transfusion. The study of TRALI has been hampered by inadequate case definitions and an incomplete understanding of the pathologic mechanisms. Recent consensus conferences took an important first step by providing a framework for case definition. Recent advances in the understanding of the pathogenesis of TRALI have also occurred. TRALI has been primarily attributed to donor leukocyte antibodies that are thought to interact with recipient neutrophils, resulting in activation and aggregation in pulmonary capillaries, release of local biologic response modifiers causing capillary leak, and lung injury. An alternate mechanism termed the "two hit" or "neutrophil priming" hypothesis postulates that a pathway to neutrophil activation and aggregation can occur without leukocyte antibodies. A first event such as sepsis or trauma can induce pulmonary endothelial activation, release of cytokines, and priming of neutrophils. A subsequent second event such as exposure to lipids, cytokines or antibodies in a blood component would then cause activation of adherent neutrophils and a release of bioreactive molecules leading to lung injury. There are limited clinical and animal studies to support the "two hit" model. These proposed mechanisms are not mutually exclusive in that donor leukocyte antibody can be pathogenic in both models and have implications for new strategies to prevent TRALI.Advances in blood safety have greatly reduced the risk of transfusion-associated infectious disease transmission. As a result, noninfectious serious hazards of transfusion have come to the forefront as increasingly important blood safety issues. Transfusion-associated acute lung injury (TRALI) has emerged as a leading cause of transfusion related morbidity and mortality.1 This report will summarize recent consensus conferences that have provided practical clinical definitions of TRALI to aid the clinician in diagnosis and to facilitate its study. Recent advances in understanding of the pathogenesis of TRALI will be presented with a potential unifying hypothesis. DefinitionA lack of a standardized definition of TRALI has hindered accurate clinical diagnosis, epidemiology, and research investigation. A recent NHLBI working group convened to identify research needs addressed this critical issue by providing the following definition: "new acute lung injury (ALI) occurring during or within 6 hours after a transfusion, with a clear temporal relationship to transfusion, in patients without or with risk factors for ALI other than transfusion."2 Limitations to the proposed NHLBI working group definition are the exclusion of patients with preexisting ALI, excluding cases with onset more than 6 hours after transfusion, lack of laboratory diagnostic criteria, and a required severity of hypoxia that would miss cases of mil...

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HLA class II antibodies in transfusion‐related acute lung injury

Cited by 211 publications

References 35 publications

The pathogenesis of transfusion‐related acute lung injury (TRALI)

The pathogenesis of transfusion‐related acute lung injury (TRALI)

Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo

Transfusion-Related Acute Lung Injury: An Update

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