ArticlePloS one2016
Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The absence of ADAMTS13 improves early outcomes in an experimental model of trauma with uncontrolled hemorrhage.The journal of trauma and acute care surgery · 2026Article
- A novel role for ADAMTS13 in hyperfibrinolysis after trauma-induced shockBritish journal of anaesthesia · 2026Article
- Animal models for thrombotic thrombocytopenic purpura: a narrative review.Annals of blood · 2023Article
- Immune-mediated thrombotic thrombocytopenic purpura plasma induces calcium- and IgG-dependent endothelial activation: correlations with disease severity.Haematologica · 2023Article
- Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?Journal of clinical medicine · 2023Review
- ADAMTS13 conformations and mechanism of inhibition in immune thrombotic thrombocytopenic purpura.Journal of thrombosis and haemostasis : JTH · 2022Review
- Article
- Autoimmune-mediated renal disease and hypertension.Clinical science (London, England : 1979) · 2021Review
- Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis.Blood advances · 2021Observational
- Animal models of thrombotic thrombocytopenic purpura: the tales from zebrafish.Haematologica · 2020Article
- von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome.Journal of thrombosis and haemostasis : JTH · 2019Article
- Dissecting the pathophysiology of immune thrombotic thrombocytopenic purpura: interplay between genes and environmental triggers.Haematologica · 2018Review
- ADAMTS-13 and von Willebrand factor: a dynamic duo.Journal of thrombosis and haemostasis : JTH · 2018Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68-90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease.
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