ArticleBlood2014
High-resolution mapping of epitopes on the C2 domain of factor VIII by analysis of point mutants using surface plasmon resonance.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
23 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- Comprehensive Screening of Genetic Variants in the Coding Region ofLife (Basel, Switzerland) · 2024Article
- Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort.Blood advances · 2024Article
- Anti-FVIII antibodies in Black and White hemophilia A subjects: do F8 haplotypes play a role?Blood advances · 2023Article
- Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner.Frontiers in immunology · 2023Article
- Removal of single-site N-linked glycans on factor VIII alters binding of domain-specific monoclonal antibodies.Journal of thrombosis and haemostasis : JTH · 2022Article
- Stable binding to phosphatidylserine-containing membranes requires conserved arginine residues in tandem C domains of blood coagulation factor VIII.Frontiers in molecular biosciences · 2022Article
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Evaluation of anti-factor VIII antibody levels in patients with haemophilia A receiving immune tolerance induction therapy or bypassing agents.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Article
- Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.Antibodies (Basel, Switzerland) · 2018Review
- FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity.Blood advances · 2018Article
- Predicting CD4 T-cell epitopes based on antigen cleavage, MHCII presentation, and TCR recognition.PloS one · 2018Article
- The structural basis for the functional comparability of factor VIII and the long-acting variant recombinant factor VIII Fc fusion protein.Journal of thrombosis and haemostasis : JTH · 2017Article
- Antibody Engineering for Pursuing a Healthier Future.Frontiers in microbiology · 2017Review
- Review
- Article
- Engineering less immunogenic and antigenic FVIII proteins.Cellular immunology · 2016Review
- Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay.Journal of thrombosis and haemostasis : JTH · 2015Article
- Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Neutralizing anti-factor VIII (FVIII) antibodies that develop in patients with hemophilia A and in murine hemophilia A models, clinically termed "inhibitors," bind to several distinct surfaces on the FVIII-C2 domain. To map these epitopes at high resolution, 60 recombinant FVIII-C2 proteins were generated, each having a single surface-exposed residue mutated to alanine or a conservative substitution. The binding kinetics of these muteins to 11 monoclonal, inhibitory anti-FVIII-C2 antibodies were evaluated by surface plasmon resonance and the results compared with those obtained for wild-type FVIII-C2. Clusters of residues with significantly altered binding kinetics identified "functional" B-cell epitopes, defined as those residues contributing appreciable antigen-antibody avidity. These antibodies were previously shown to neutralize FVIII activity by interfering with proteolytic activation of FVIII by thrombin or factor Xa, or with its binding to phospholipid surfaces, von Willebrand factor, or other components of the intrinsic tenase complex. Fine mapping of epitopes by surface plasmon resonance also indicated surfaces through which FVIII interacts with proteins and phospholipids as it participates in coagulation. Mutations that significantly altered the dissociation times/half-lives identified functionally important interactions within antigen-antibody interfaces and suggested specific sequence modifications to generate novel, less antigenic FVIII proteins with possible therapeutic potential for treatment of inhibitor patients.
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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.