ArticleBlood2018
Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Platelet desialylation, apoptosis, and T-lymphocyte-mediated immune dysregulation: unveiling the pathways of platelet clearance in platelet transfusion refractoriness.Research and practice in thrombosis and haemostasis · 2026Article
- Platelet dysfunction in immune thrombocytopenia: Finding clinical subsets with platelet phenotypes.British journal of haematology · 2026Article
- Kupffer cells are essential for platelet-mediated thrombopoietin generation in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Many Faces of Immune Thrombocytopenia: Mechanisms, Therapies, and Clinical Challenges in Oncological Patients.Journal of clinical medicine · 2024Review
- GPIbα CAAR T cells function like a Trojan horse to eliminate autoreactive B cells to treat immune thrombocytopenia.Haematologica · 2024Article
- Successful treatment with oseltamivir phosphate in children with ITP who failed first-line therapy: a case series report.Annals of hematology · 2024Article
- The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives.Frontiers in immunology · 2024Review
- Pathogenesis of refractory ITP: Overview.British journal of haematology · 2023Review
- Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain.Blood · 2023Article
- Intracavitary cardiac metastasis of cervical squamous cell carcinoma with immune thrombocytopenia: a rare case report.Frontiers in oncology · 2023Article
- SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.Research (Washington, D.C.) · 2023Article
- Recent advances on GPIb-IX-V complex.Platelets · 2022Article
- Fast clearance of platelets in a commonly used mouse model for GPIbα is impeded by an anti-GPIbβ antibody derivative.Journal of thrombosis and haemostasis : JTH · 2022Article
- Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.Medicina (Kaunas, Lithuania) · 2022Review
- Review
- Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.Journal of thrombosis and haemostasis : JTH · 2021Article
- GPIbα is the driving force of hepatic thrombopoietin generation.Research and practice in thrombosis and haemostasis · 2021Article
- Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management.Journal of clinical medicine · 2021Review
- Structure-function of platelet glycoprotein Ib-IX.Journal of thrombosis and haemostasis : JTH · 2020Review
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Immune thrombocytopenia (ITP) is a prevalent autoimmune disease characterized by autoantibody-induced platelet clearance. Some ITP patients are refractory to standard immunosuppressive treatments such as intravenous immunoglobulin (IVIg). These patients often have autoantibodies that target the ligand-binding domain (LBD) of glycoprotein Ibα (GPIbα), a major subunit of the platelet mechanoreceptor complex GPIb-IX. However, the molecular mechanism of this Fc-independent platelet clearance is not clear. Here, we report that many anti-LBD monoclonal antibodies such as 6B4, but not AK2, activated GPIb-IX in a shear-dependent manner and induced IVIg-resistant platelet clearance in mice. Single-molecule optical tweezer measurements of antibodies pulling on full-length GPIb-IX demonstrated that the unbinding force needed to dissociate 6B4 from the LBD far exceeds the force required to unfold the juxtamembrane mechanosensory domain (MSD) in GPIbα, unlike the AK2-LBD unbinding force. Binding of 6B4, not AK2, induced shear-dependent unfolding of the MSD on the platelet, as evidenced by increased exposure of a linear sequence therein. Imaging flow cytometry and aggregometry measurements of platelets and LBD-coated platelet-mimetic beads revealed that 6B4 can sustain crosslinking of platelets under shear, whereas 6B4 Fab and AK2 cannot. These results suggest a novel mechanism by which anti-LBD antibodies can exert a pulling force on GPIb-IX via platelet crosslinking, activating GPIb-IX by unfolding its MSD and inducing Fc-independent platelet clearance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.