Observational studyThe New England journal of medicine2026
Adenoviral Inciting Antigen and Somatic Hypermutation in VITT.
Observational study in The New England journal of medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Investigation and systematic review of temporal associations between vaccination and onset of immune-mediated hemolytic anemia or thrombocytopenia in dogs.Journal of veterinary internal medicine · 2026Pooled it
- Autoimmune-associated thrombosis: mechanisms, population burden, and prevention strategies.The Lancet regional health. Europe · 2026Review
- Charge-driven antiviral responses enhance autoreactivity in severe COVID-19.Research square · 2026Article
- Non-PF4/heparin-binding, platelet-activating antibodies in heparin-induced thrombocytopenia.Blood · 2026Article
- Platelet factor 4 antibody persistence and long-term pathogenicity in vaccine-induced immune thrombotic thrombocytopenia.Journal of thrombosis and haemostasis : JTH · 2026Article
- Xenosialylation as immunological chimerism: a host-centered unifying model for viral and post-vaccination immune complications.European cytokine network · 2026Review
- Solving the mystery of vaccine-induced immune thrombocytopenia and thrombosis.Nature reviews. Cardiology · 2026Article
- Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): An Immunopathogenic Model of Dysregulated Vaccine-Triggered Immunity.Vaccines · 2026Review
- Article
- Autophagy, NET formation, and inflammation crosstalk in thrombotic autoimmune diseases.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
backgroundVaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare prothrombotic complication that occurs after adenoviral vector-based vaccination against coronavirus disease 2019; in rare cases, it can also occur after natural adenovirus infection. VITT is mediated by platelet-activating antibodies against the highly cationic protein platelet factor 4 (PF4). The underlying inciting antigen trigger and immunopathogenesis remain unknown.
methodsWe used antibody proteomics to determine the amino acid sequences of anti-PF4 antibodies from 21 patients with VITT and sequenced the genes encoding the immunoglobulin light-chain hypervariable region from 100 patients with VITT. To identify an adenoviral trigger, we used the antigen-binding fingerprints of anti-PF4 and anti-adenovirus protein antibodies to identify a shared serum clonotype and subsequently used adenovirus protein peptides and recombinant anti-PF4 VITT antibodies to map the mimicking linear epitope.
resultsGenomic and proteomic profiling of VITT antibodies revealed a shared immunoglobulin light-chain allele, IGLV3-21*02 or *03, harboring a critical somatic hypermutation, K31E. Only antibodies purified against adenoviral core protein VII (pVII) contained anti-PF4 species matching the VITT fingerprint; antibodies against intact virions or other adenoviral proteins did not. Cross-reactive IgGs were mapped to a basic linear epitope on pVII. A pathogenic anti-PF4 VITT antibody, back-mutated to germline (K31), lost its prothrombotic activity in vitro and in vivo and preferentially bound pVII, a finding that directly supported the role of the hypermutation in the antigenic shift from adenovirus pVII to PF4.
conclusionsThe results of our study indicate that VITT occurs when, in persons with immunoglobulin light-chain allele IGLV3-21*02 or *03, a specific somatic hypermutation develops that affects antibodies that recognize a specific epitope on the adenoviral core protein pVII, which results in misdirection of antibody targeting toward PF4. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00025738; EU Post-Authorization Study Register number, EUPAS45098.).
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