In vitro characterization of rare anti-αβ isoantibodies produced by patients with Glanzmann thrombasthenia that severely block fibrinogen binding and generate procoagulant platelets via complement activation.
| dc.rights.license | open | en_US |
| dc.contributor.author | LEE, Christine S M | |
| dc.contributor.author | HUGUENIN, Yoann | |
| dc.contributor.author | PILLOIS, Xavier | |
| dc.contributor.author | MOULIERAS, Mikeldi | |
| dc.contributor.author | MARCY, Ella | |
| dc.contributor.author | WHITTAKER, Shane | |
| dc.contributor.author | CHEN, Vivien M Y | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | FIORE, Mathieu | |
| dc.date.accessioned | 2024-03-11T14:53:30Z | |
| dc.date.available | 2024-03-11T14:53:30Z | |
| dc.date.issued | 2024-01-01 | |
| dc.identifier.issn | 2475-0379 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/188688 | |
| dc.description.abstractEn | Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet αβ integrin. Platelet transfusions can be followed by an immune response that can block integrin function by interfering with fibrinogen binding. In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. Twelve patients with GT were evaluated for anti-αβ isoantibodies. Sera from patients with GT with or without anti-αβ isoantibodies were then used to study their effect on platelets from healthy donors. We used several approaches (IgG purification, immunofluorescence staining, and inhibition of signaling pathways) to characterize the pathogenic properties of the anti-αβ isoantibodies. Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins. Our data suggest that complement activation induced by rare blocking anti-αβ isoantibodies may lead to the formation of a MAC with subsequent pore formation, resulting in calcium influx and procoagulant platelet phenotype. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject | article clinique | |
| dc.subject.en | Glanzmann thrombasthenia; anti-αIIbβ3 isoantibodies; coagulation; complement activation; platelet transfusion; procoagulant platelet | |
| dc.title.en | In vitro characterization of rare anti-αβ isoantibodies produced by patients with Glanzmann thrombasthenia that severely block fibrinogen binding and generate procoagulant platelets via complement activation. | |
| dc.title.alternative | Res Pract Thromb Haemost | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.rpth.2023.102253 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.identifier.pubmed | 38268518 | en_US |
| bordeaux.journal | Research and Practice in Thrombosis and Haemostasis | en_US |
| bordeaux.page | 102253 | en_US |
| bordeaux.volume | 8 | en_US |
| bordeaux.hal.laboratories | Biologie des maladies cardiovasculaires (BMC) - UMR 1034 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
| hal.identifier | hal-04499921 | |
| hal.version | 1 | |
| hal.date.transferred | 2024-03-11T14:53:33Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Research%20and%20Practice%20in%20Thrombosis%20and%20Haemostasis&rft.date=2024-01-01&rft.volume=8&rft.issue=1&rft.spage=102253&rft.epage=102253&rft.eissn=2475-0379&rft.issn=2475-0379&rft.au=LEE,%20Christine%20S%20M&HUGUENIN,%20Yoann&PILLOIS,%20Xavier&MOULIERAS,%20Mikeldi&MARCY,%20Ella&rft.genre=article |
