Human alloantibody anti-Mart interferes with Mac-1–dependent leukocyte adhesion

Sachs, Ulrich J.; Chavakis, Triantafyllos; Fung, Yoke Lin; Lohrenz, Alexander; Bux, Jürgen; Reil, Angelika; Ruf, Andreas; Santoso, Sentot

doi:10.1182/blood-2003-11-3809

Cited by 49 publications

(61 citation statements)

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“…We and others have demonstrated that antibodies to neutrophilspecific antigens involved in TRALI cases are able to prime and even activate neutrophils as well (Kopko et al, 2004;Sachs et al, 2004;Sachs et al, 2006;Silliman et al, 2006). This, as discussed below, explains why even completely healthy individuals can develop TRALI upon neutrophil antibody infusion (Dooren et al, 1998).…”

Section: Consequences Of Circulating Primed Neutrophils With Regard Tmentioning

confidence: 88%

“…In addition, it has to be kept in mind that antibodies of the same specificity are not always functionally alike, as we have demonstrated for human antibodies recognising HNA-4a on CD11b. Some of these antibodies were capable of inducing the respiratory burst reaction, whereas others were not, although their serological reactivity was identical (Sachs et al, 2004). It should thus not be excluded that antibodies to HLA class I, besides their possible role in trapping neutrophils via Fc receptors and activating the pulmonary endothelium, can also prime and/or activate neutrophils; currently, there are only case reports from neutrophil transfusions indicating that HLA antibodies are capable of interacting with neutrophils directly (see below), and this issue awaits further experimental clarification.…”

Section: Antibodies To Human Leucocyte Antigensmentioning

confidence: 98%

“…It seems reasonable to speculate that antibodies to HNA-3a were capable of priming and activating neutrophils in the model published by Seeger et al (1990). Indeed, it was demonstrated recently that HNA-3a antibodies are able to prime neutrophils in vitro (Kopko et al, 2004;Silliman et al, 2006), as are antibodies to HNA4a and HNA-2a (Sachs et al, 2004;Sachs et al, 2006). Antibodies directed against the neutrophil-specific surface marker CD177 (HNA-2a) were recently used by ourselves to demonstrate that TRALI induction in an ex vivo rat lung model is dependent on the density of the cognate antigen and can be enhanced efficiently by the addition of fMLP, a substance that mimics the activity of bacterially derived peptides and is used to approximate active infection (Sachs et al, 2006).…”

Section: Antibodies To Human Neutrophil Antigensmentioning

confidence: 99%

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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: Consequences Of Circulating Primed Neutrophils With Regard Tmentioning

confidence: 88%

Section: Antibodies To Human Leucocyte Antigensmentioning

confidence: 98%

Section: Antibodies To Human Neutrophil Antigensmentioning

confidence: 99%

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

2007

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“…It is generally thought, although unproven, that either receptor cross-linking or direct activation of the receptor may lead to signaling events that cause neutrophil activation and, subsequent, deterioration of the lung vascular integrity. 10,13,32,33 This mechanism is not likely in the case of HLA class II antibodies, because HLA class II antigens are normally not present on neutrophils (see below). Here, we observed, however, that HLA class II antibodies can bind to monocytes that express the cognate antigen and thereby induces the release of potent cytokines and LTB 4 .…”

Section: Discussionmentioning

confidence: 99%

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies

Sachs

Wasel

Bayat

et al. 2011

Blood

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Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II-induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody-dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibodyinduced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures. (Blood. 2011;117(2):669-677) IntroductionTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated death in the United States and other countries. 1 It typically presents within 6 hours after transfusion as a clinical syndrome characterized by acute respiratory distress, hypoxemia, and a bilateral pulmonary edema on chest x-ray. 2 The incidence of TRALI has been estimated as 1/5000 for all blood components, and current mortality rates are in the range of 5%-25%. 3 All blood components have been implicated in TRALI, but those containing large amounts of plasma are mainly responsible. [3][4][5] A recently published literature review states that in 80% of all TRALI cases, white blood cell antibodies can be identified in the implicated blood donor, 6 and most implicated donors have been women with a history of pregnancy. Pregnancy results in alloimmunization against paternal white blood cell antigens in 21%-24% of women, 7,8 with 3 main antibody specificities: human leukocyte antigen (HLA) class I, HLA class II, and human neutrophil antigens (HNAs).The capability of antibodies recognizing either HNA 9-11 or HLA class I 12,13 to precipitate TRALI has been proved in different animal models. It is consensus opinion that neutrophil activation is the key mechanism by which antibodies to HNA and to HLA class I mediate TRALI, 4,14 be it by direct binding to the cognate antigen on the surface of the neutrophil [9][10][11]13 or, in the case of HLA class I antibodies, possibly by binding to HLA class I molecules on pulmonary endothelial cells, which leads to neutrophil trapping by the neutrophils' Fc receptors and subsequent neutrophil activation by receptor...

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“…HNA-4a alloantibodies can cause neonatal immune neutropenia . Two types of HNA-4a antisera have been identified, with different effects in cell interactions, suggesting that the humoral response to this antigen is heterogeneous and differs from one immunized person to another (Sachs et al 2004). The CD11b/CD18 is also the target of autoantibodies reported not only to cause neutropenia, but also to be able to impair neutrophil adhesion (Hartman and Wright 1991).…”

Section: Biochemistry and Molecular Basismentioning

confidence: 99%

Human neutrophil alloantigens systems

Moritz

Norcia

Cardone

et al. 2009

An. Acad. Bras. Ciênc.

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Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusionrelated acute lung injury (TRALI), refractoriness to granulocyte transfusions and febrile transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. Currently, seven antigens are assigned to five human neutrophil antigen (HNA) systems. The HNA-1a, HNA-1b and HNA-1c antigens have been identified as polymorphic forms of the neutrophil Fcγ receptor IIIb (CD16b), encoded by three alleles. Recently, the primary structure of the HNA-2a antigen was elucidated and the HNA-2a-bearing glycoprotein was identified as a member of the Ly-6/uPAR superfamily, which has been clustered as CD177. The HNA-3a antigen is located on a 70-95 kDa glycoprotein; however, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens were found to be caused by single nucleotide mutations in the α M (CD11b) and α L (CD11a) subunits of the leucocyte adhesion molecules (β 2 integrins). Molecular and biochemical characterization of neutrophil antigens have expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. Further studies in the field of neutrophil immunology will facilitate the prevention and management of transfusion reactions and immune diseases caused by neutrophil antibodies.

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Human alloantibody anti-Mart interferes with Mac-1–dependent leukocyte adhesion

Abstract: The CD11b/CD18 integrin plays a crucial role in cell-cell adhesion processes. Recently, we described a case of severe neonatal alloimmune neutropenia (

Cited by 49 publications

References 49 publications

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

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

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies

Human neutrophil alloantigens systems

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