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10.1182/blood.2021012938

http://scihub22266oqcxt.onion/10.1182/blood.2021012938
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suck abstract from ncbi


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pmid34280256      Blood 2021 ; 138 (14): 1269-1277
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  • Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein #MMPMID34280256
  • Greinacher A; Selleng K; Mayerle J; Palankar R; Wesche J; Reiche S; Aebischer A; Warkentin TE; Muenchhoff M; Hellmuth JC; Keppler OT; Duerschmied D; Lother A; Rieg S; Gawaz MP; Mueller KAL; Scheer CS; Napp M; Hahnenkamp K; Lucchese G; Vogelgesang A; Floel A; Lovreglio P; Stufano A; Marschalek R; Thiele T
  • Blood 2021[Oct]; 138 (14): 1269-1277 PMID34280256show ga
  • Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcgammaRIIa receptors. Antibodies that activate platelets through FcgammaRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Antibodies/*adverse effects[MESH]
  • |Blood Platelets/immunology[MESH]
  • |COVID-19 Vaccines/*adverse effects[MESH]
  • |COVID-19/immunology[MESH]
  • |Cohort Studies[MESH]
  • |Cross Reactions/*immunology[MESH]
  • |Epitopes/immunology[MESH]
  • |Female[MESH]
  • |Heparin/metabolism[MESH]
  • |Humans[MESH]
  • |Immunoglobulin G/immunology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Platelet Factor 4/*immunology[MESH]
  • |Protein Binding[MESH]
  • |Protein Domains[MESH]
  • |Purpura, Thrombocytopenic, Idiopathic/blood/*etiology/*immunology[MESH]
  • |Spike Glycoprotein, Coronavirus/chemistry/*immunology[MESH]


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