ArticleBlood2013
The diversity of the immune response to the A2 domain of human factor VIII.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
- Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides.Haematologica · 2025Article
- Persistent splenic-derived IgMs preferentially recognize factor VIII A2 and C2 domain epitopes but do not alter antibody production.Journal of thrombosis and haemostasis : JTH · 2025Article
- Review
- Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner.Frontiers in immunology · 2023Article
- Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.Research and practice in thrombosis and haemostasis · 2022Article
- Removal of single-site N-linked glycans on factor VIII alters binding of domain-specific monoclonal antibodies.Journal of thrombosis and haemostasis : JTH · 2022Article
- Novel Coagulation Factor VIII Gene Therapy in a Mouse Model of Hemophilia A by Lipid-Coated FeBiomedicines · 2021Article
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Plasma-derived factors VIIa and X mixtures (ByclotInternational journal of hematology · 2020Article
- The 3.2 Å structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain.Journal of thrombosis and haemostasis : JTH · 2020Article
- Sedimentation Velocity Analytical Ultracentrifugation of Oxidized Recombinant Full-Length Factor VIII.Frontiers in immunology · 2020Article
- Recombinant Factor VIII Fc Inhibits B Cell Activation via Engagement of the FcγRIIB Receptor.Frontiers in immunology · 2020Article
- Plant cell-made protein antigens for induction of Oral tolerance.Biotechnology advances · 2019Review
- Infused factor VIII-expressing platelets or megakaryocytes as a novel therapeutic strategy for hemophilia A.Blood advances · 2019Article
- Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A.Human gene therapy · 2018Article
- Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.Antibodies (Basel, Switzerland) · 2018Review
- Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction.Nature biotechnology · 2017Article
- Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Approximately 30% of patients with severe hemophilia A develop inhibitory anti-factor VIII (fVIII) antibodies (Abs). We characterized 29 anti-human A2 monoclonal Abs (mAbs) produced in a murine hemophilia A model. A basis set of nonoverlapping mAbs was defined by competition enzyme-linked immunosorbent assay, producing 5 major groups. The overlapping epitopes covered nearly the entire A2 surface when mapped by homolog-scanning mutagenesis. Most group A mAbs recognized a previously described epitope bounded by Arg484-Ile508 in the N-terminal A2 subdomain, resulting in binding to activated fVIII and noncompetitive inhibition of the intrinsic fXase complex. Group B and C mAbs displayed little or no inhibitory activity. Group D and E mAbs recognized epitopes in the C-terminal A2 subdomain. A subset of group D mAbs inhibited the activation of fVIII by interfering with thrombin-catalyzed cleavage at Arg372 at the A1-A2 domain junction. Other group D mAbs displayed indeterminate or no inhibitory activity despite inhibiting cleavage at Arg740 at the A2-B domain junction. Group E mAbs inhibited fVIII light-chain cleavage at Arg1689. Inhibition of cleavages at Arg372 and Arg1689 represent novel mechanisms of inhibitor function and, along with the extensive epitope spectrum identified in this study, reveal hitherto unrecognized complexity in the immune response to fVIII.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.