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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-42190

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 activate platelets in the absence of heparin. Here we show that antibodies with binding forces of approximately 60–100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-HIT patients with binding forces Z100 pN binds to PF4 alone in the absence of polyanions. These antibodies with high binding forces cluster PF4-molecules forming antigenic complexes which allow binding of polyanion-dependent anti-PF4/P-antibodies. The resulting immunocomplexes induce massive platelet activation in the absence of heparin. Antibody-mediated changes in endogenous proteins that trigger binding of otherwise non-pathogenic (or cofactor-dependent) antibodies may also be relevant in other antibody-mediated autoimmune disorders.

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Metadaten
Author: Thi-Huong Nguyen, Nikolay Medvedev, Mihaela Delcea, Andreas Greinacher
URN:urn:nbn:de:gbv:9-opus-42190
ISSN:2041-1723
Parent Title (English):Nature Communications
Document Type:Article
Language:English
Year of Completion:2017
Release Date:2020/12/22
Volume:8
First Page:14945
Faculties:Mathematisch-Naturwissenschaftliche Fakultät
Licence (German):License LogoCreative Commons - Namensnennung