Anti‐annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

Matsuda, Juzo; Saitoh, Noriko; Gohchi, Kengo; Gotoh, Moritaka; Tsukamoto, Mitsuo

doi:10.1002/ajh.2830470112

Cited by 121 publications

(53 citation statements)

References 7 publications

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“…These auto-antibodies are heterogeneous, and encompass a broad range of target specificities and affinities, all recognizing various combinations of phospholipids and/or phospholipid-binding proteins [2,3]. While aPL were initially believed to target anionic phospholipids directly, we now appreciate that aPL recognize primarily phospholipid-binding proteins that interact with anionic phospholipids, such as β2-glycoprotein I (β2GPI), prothrombin (PT), and annexin V [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Anti-phospholipid antibodies (aPL) and apoptosis: prothrombin-dependent aPL as a paradigm for phospholipid-dependent interactions with apoptotic cells

Rauch

D’Agnillo

Subang

et al. 2004

Thrombosis Research

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The natural targets of anti-phospholipid antibodies (aPL) and the stimuli that induce them remain unknown. Apoptotic cells have been proposed as both potential targets and immunogens for antiphospholipid antibodies. Demonstration of selective recognition by anti-phospholipid antibodies provides support for apoptotic cells as antigenic targets. Here, we summarize data showing that prothrombin (PT) binds to apoptotic, but not viable, cells, and that apoptotic-cell bound prothrombin provides a target for human polyclonal and murine monoclonal lupus anticoagulant (LA) antibodies. We discuss findings for two monoclonal lupus anticoagulant antibodies that have high (antibody 29J3-62) or low (antibody 29I4-24) affinity, respectively, for soluble prothrombin. Despite their very different affinities for soluble prothrombin, both monoclonal antibodies reacted similarly with prothrombin bound to phospholipid or apoptotic cells. Furthermore, both antibodies enhanced the binding of prothrombin to apoptotic cells. We propose that the recognition of apoptotic cells by these prothrombin-dependent monoclonal antibodies provides a paradigm for other anti-phospholipid autoantibodies. 29I4-24 is prototypical of phospholipid-dependent antiphospholipid antibodies, while 29J3-62 represents a prototype for phospholipid-independent antiphospholipid antibodies. Proteins such as prothrombin and β2-glycoprotein I (β2GPI) bind to apoptotic cells, thereby enhancing the recognition of apoptotic cells by anti-phospholipid antibodies. Furthermore, anti-phospholipid antibodies potentiate the interaction of these proteins with apoptotic cells. While it is unclear whether apoptotic cells are the inducing stimuli in patients with anti-phospholipid antibodies or even whether anti-phospholipid antibodies interact with apoptotic cells in vivo, it is nonetheless clear that anti-phospholipid antibodies have the potential to affect both the procoagulant activity and the uptake and clearance of apoptotic cells.

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Section: Introductionmentioning

confidence: 99%

Anti-phospholipid antibodies (aPL) and apoptosis: prothrombin-dependent aPL as a paradigm for phospholipid-dependent interactions with apoptotic cells

Rauch

D’Agnillo

Subang

et al. 2004

Thrombosis Research

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“…They are associated with a clinical syndrome of thrombosis and/or recurrent fetal loss (1,2). Although aPL were initially believed to target anionic phospholipids (PL) directly, they are now thought to recognize primarily PL-binding proteins that interact with anionic PL, such as ␤ 2 -glycoprotein I (␤ 2 GPI), annexin V, and prothrombin (PT) (3)(4)(5)(6)(7). Recent work has shown that certain aPL recognize these PL-binding proteins alone, whereas other aPL require the presence of PL for this recognition (8 -10).…”

mentioning

confidence: 99%

Prothrombin Binds to the Surface of Apoptotic, But Not Viable, Cells and Serves as a Target of Lupus Anticoagulant Autoantibodies

D’Agnillo

Levine

Subang

et al. 2003

The Journal of Immunology

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Anti-phospholipid Ab (aPL) are a heterogeneous group of autoantibodies directed against various combinations of phospholipids (PL) and PL-binding proteins. Lupus anticoagulant (LA) Ab, a subset of aPL, exhibit anticoagulant properties in vitro, but are procoagulant in vivo. Most LA Ab are specific for either β2-glycoprotein I (β2GPI) or prothrombin (PT), two PL-binding proteins. We have previously shown that β2GPI and β2GPI-dependent aPL bind specifically to apoptotic, but not viable, thymocytes. In this study, we demonstrate that PT, like β2GPI, binds selectively to the surface of apoptotic, but not viable, Jurkat cells. Furthermore, PT supports the binding of systemic lupus erythematosus-derived polyclonal and murine monoclonal LA Ab to apoptotic cells. Two LA mAb, which differed dramatically in their relative affinities for PT, were studied. Although one mAb (29J3-62) had a high affinity for PT alone, the other (29I4-24) showed minimal reactivity with PT alone and required PL for elevated binding. Monovalent fragments of 29I4-24 reacted with PL-bound PT with high affinity, suggesting that this mAb recognizes a PL-dependent epitope. Despite these differences, PT-dependent binding of both mAb to apoptotic cells was 30-fold greater than that to viable cells. Moreover, binding of PT to apoptotic cells was, itself, increased in the presence of bivalent, but not monovalent, forms of either mAb. In summary, our data demonstrate the following: 1) specific binding of PT to apoptotic cells, an effect enhanced by PT-dependent LA Ab; 2) heterogeneity of PT-dependent LA Ab; and 3) potential pathogenicity of Ab of either low or high affinity for PT.

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“…In 1994, Matsuda et al [2] first described positive a-A5 in 26% of patients with systemic lupus erythematosus (SLE) and suggested that this antibody could be an independent risk factor in these patients. Three years later, Kaburaki et al [29] found positive a-A5 in 19% of SLE patients and emphasized that these antibodies are found more frequently in patients with arterial and/or venous thromboses, intrauterine fetal loss and prolonged APTT, as well as in SLE patients with negative APL.…”

Section: Significance Of the Determination Of A-a5 In Patients With Smentioning

confidence: 99%

Diagnostic significance of anti-annexin-A5 antibody determination

2010

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AbstractAnti-annexin A5 antibodies are directed against annexin A5 — a phospholipid-binding protein that belongs to the ubiquitous annexin family. These antibodies were first discovered in 1994 by Matsuda et al. in women with recurrent fetal loss or preeclampsia and in patients with systemic lupus erythematosus and positive lupus anticoagulant and/or anticardiolipin antibodies. Since then anti-annexin A5 antibodies have been the focus of research. In addition to their well known prothrombotic and procoagulant activities the authors discuss the involvement of these antibodies in the pathogenesis of antiphospholipid syndrome, recurrent pregnancy loss, systemic lupus erythematosus and other immune and non-immune disorders. Controversial reports are presented and a possible interpretation of the results is given. The authors suggest the significance of anti-annexin A5 antibodies as an additional diagnostic marker and discuss the necessity of more extensive research on their clinical significance.

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Anti‐annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

Cited by 121 publications

References 7 publications

Anti-phospholipid antibodies (aPL) and apoptosis: prothrombin-dependent aPL as a paradigm for phospholipid-dependent interactions with apoptotic cells

Anti-phospholipid antibodies (aPL) and apoptosis: prothrombin-dependent aPL as a paradigm for phospholipid-dependent interactions with apoptotic cells

Prothrombin Binds to the Surface of Apoptotic, But Not Viable, Cells and Serves as a Target of Lupus Anticoagulant Autoantibodies

Diagnostic significance of anti-annexin-A5 antibody determination

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