Platelet factor 4 binds to bacteria, inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia

نویسندگان

  • Krystin Krauel
  • Christian Pötschke
  • Claudia Weber
  • Wolfram Kessler
  • Birgitt Fürll
  • Till Ittermann
  • Stefan Maier
  • Sven Hammerschmidt
  • Barbara M. Bröker
  • Andreas Greinacher
چکیده

1Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Greifswald, Germany; 2Genetik der Mikroorganismen, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität, Greifswald, Germany; 3Klinik und Poliklinik für Allgemeine Chirurgie, Viszeral-, Thoraxund Gefässchirurgie, Ernst-Moritz-Arndt Universität, Greifswald, Germany; and 4Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany

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PLATELETS AND THROMBOPOIESIS Platelet factor 4 binds to bacteria, inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia

1Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Greifswald, Germany; 2Genetik der Mikroorganismen, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität, Greifswald, Germany; 3Klinik und Poliklinik für Allgemeine Chirurgie, Viszeral-, Thoraxund Gefässchirurgie, Ernst-Moritz-Arndt Universität, Greifswald, Germany; ...

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Management of Heparin-Induced Thrombocytopenia in Uremic Patients with Hemodialysis

Unfractionated heparin is the most commonly used anticoagulant for hemodialysis (HD) (Sonawane et al., 2006). It is well-known that heparin can cause immune-mediated thrombocytopenia due to immunoglobulin antibody formation against the complex of platelet factor 4 (PF4) and heparin. Heparin may also contribute to HD-associated platelet activation, thrombocytopenia, and increased PF4 release fro...

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Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria.

Short chain polyphosphates (polyP) are pro-coagulant and pro-inflammatory platelet released inorganic polymers. The platelet chemokine platelet factor 4 (PF4) binds to lipid A on bacteria, inducing an antibody mediated host defense mechanism, which can be misdirected against PF4/heparin complexes leading to the adverse drug reaction heparin-induced thrombocytopenia (HIT). Here, we demonstrate t...

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Platelet factor 4 binding to lipid A of Gram-negative bacteria exposes PF4/heparin-like epitopes.

The positively charged chemokine platelet factor 4 (PF4) forms immunogenic complexes with heparin and other polyanions. Resulting antibodies can induce the adverse drug effect heparin-induced thrombocytopenia. PF4 also binds to bacteria, thereby exposing the same neoantigen(s) as with heparin. In this study, we identified the negatively charged lipopolysaccharide (LPS) as the PF4 binding struct...

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Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity

Antibodies recognizing complexes of the chemokine platelet factor 4 (PF4/CXCL4) and polyanions (P) opsonize PF4-coated bacteria hereby mediating bacterial host defense. A subset of these antibodies may activate platelets after binding to PF4/heparin complexes, causing the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). In autoimmune-HIT, anti-PF4/P-antibodies activat...

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تاریخ انتشار 2011