Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody

Jing Jing Wang, Bridie Armour , Tim Chataway, Alexander Troelnikov, Alex Colella, Olivia Yacoub, Simon Hockley, Chee Wee Tan, Tom Paul Gordon

Research output: Contribution to journalLetterpeer-review

4 Citations (Scopus)

Abstract

The syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare thromboembolic complication of adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) mediated by antibodies directed against platelet factor 4 (PF4).1-5 The mechanisms by which the adenoviral DNA vectors break immune tolerance to PF4 and trigger B-cell clonal expansion and secretion of anti-PF4 immunoglobulin Gs (IgGs) are under intense investigation and likely involve formation of immunogenic complexes of PF4 with vaccine components in a proinflammatory setting.6 Pathogenic anti-PF4 IgGs subsequently form circulating immune complexes with PF4 tetramers, which are thought to drive thrombotic events by Fc γ receptor IIa–dependent platelet activation and to activate granulocytes to release procoagulant neutrophil extracellular traps.6-8 Serum anti-PF4 antibodies are mostly transient and appear in serum within days of vaccination, suggesting...
Original languageEnglish
Pages (from-to)1738-1742
Number of pages5
JournalBlood
Volume140
Issue number15
Early online date3 Jun 2022
DOIs
Publication statusPublished - 13 Oct 2022

Keywords

  • vaccine
  • immune
  • vaccine-induced immune thrombotic thrombocytopenia
  • VITT
  • coronavirus 2
  • SARS-CoV-2
  • stereotyped clonotypic antibody

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