ArticleThe American journal of pathology2003
Human monoclonal antiphospholipid antibodies disrupt the annexin A5 anticoagulant crystal shield on phospholipid bilayers: evidence from atomic force microscopy and functional assay.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 156 citations in OpenAlex.
- Trial
- Immunoglobulin-mediated immune dysregulation in recurrent pregnancy loss: mechanisms, biomarkers, and therapeutic perspectives.Immunologic research · 2026Review
- Anti-Annexin A5 antibodies and Annexin A5 resistance in antiphospholipid syndrome: A systematic review and meta-analysis.Journal of translational autoimmunity · 2026Review
- Immune-mediated mechanisms and maternal-fetal interface dysfunction in obstetric antiphospholipid syndrome.Frontiers in immunology · 2025Review
- Thrombotic Microangiopathy in Pregnancy: Current Understanding and Management Strategies.Kidney international reports · 2024Review
- Cellular Labeling of Phosphatidylserine Using Clickable Serine Probes.ACS chemical biology · 2023Article
- Association between ANXA5 haplotypes and the risk of recurrent pregnancy loss.The Journal of international medical research · 2022Article
- Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome.Seminars in immunopathology · 2022Review
- Long-circulating XTEN864-annexin A5 fusion protein for phosphatidylserine-related therapeutic applications.Apoptosis : an international journal on programmed cell death · 2021Article
- Antiphospholipid syndrome.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Annexin-A5 resistance and non-criteria antibodies for the diagnosis of seronegative antiphospholipid syndrome.Clinical rheumatology · 2020Article
- Advances in the Research on Anticardiolipin Antibody.Journal of immunology research · 2019Review
- Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women.Arthritis research & therapy · 2018Article
- Reimagining the antiphospholipid syndrome, an enigmatic thrombophilic disorder, through the looking glass of microscopic imaging.Histochemistry and cell biology · 2018Review
- Diagnosis and management of the antiphospholipid syndrome.Blood reviews · 2017Review
- Clinical Risk Assessment in the Antiphospholipid Syndrome: Current Landscape and Emerging Biomarkers.Current rheumatology reports · 2017Review
- Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population.Journal of assisted reproduction and genetics · 2017Article
- Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome.Clinical rheumatology · 2017Article
- Circulating microparticles in patients with antiphospholipid antibodies: characterization and associations.Thrombosis research · 2015Article
- New tests to detect antiphospholipid antibodies: anti-domain I beta-2-glycoprotein-I antibodies.Current rheumatology reports · 2014Review
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 1 country.
Funding
Abstract
The antiphospholipid (aPL) syndrome is an autoimmune condition that is marked by recurrent pregnancy losses and/or systemic vascular thrombosis in patients who have antibodies against phospholipid/co-factor complexes. The mechanism(s) for pregnancy losses and thrombosis in this condition is (are) not known. Annexin A5 is a potent anticoagulant protein, expressed by placental trophoblasts and endothelial cells, that crystallizes over anionic phospholipids, shielding them from availability for coagulation reactions. We previously presented data supporting the hypothesis that aPL antibody-mediated disruption of the anticoagulant annexin A5 shield could be a thrombogenic mechanism in the aPL syndrome. However, this has remained a subject of controversy. We therefore used atomic force microscopy, a method previously used to study the crystallization of annexin A5, to image the effects of monoclonal human aPL antibodies on the crystal structure of the protein over phospholipid bilayers. In the presence of the aPL monoclonal antibodies (mAbs) and beta(2)-GPI, the major aPL co-factor, structures presumed to be aPL mAb-antigen complexes were associated with varying degrees of disruption to the annexin A5 crystallization pattern over the bilayer. In addition, measurements of prothrombinase activity on the phospholipid bilayers showed that the aPL mAbs reduced the anti-coagulant effect of annexin A5 and promoted thrombin generation. These data provide morphological evidence that support the hypothesis that aPL antibodies can disrupt annexin A5 binding to phospholipid membranes and permit increased generation of thrombin. The aPL antibody-mediated disruption of the annexin A5 anticoagulant shield may be an important prothrombotic mechanism in the aPL syndrome.
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