ArticleJournal of thrombosis and haemostasis : JTH2013
Epitope mapping of inhibitory antibodies targeting the C2 domain of coagulation factor VIII by hydrogen-deuterium exchange mass spectrometry.
Article in Journal of thrombosis and haemostasis : JTH, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- MAXTIA: A high-throughput platform for rapid functional epitope mapping by kinetic screening of mutant libraries.Protein science : a publication of the Protein Society · 2026Article
- Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort.Blood advances · 2024Article
- Structural mass spectrometry decodes domain interaction and dynamics of the full-length Human Histone Deacetylase 2.Biochimica et biophysica acta. Proteins and proteomics · 2022Article
- Computational Structure Prediction for Antibody-Antigen Complexes From Hydrogen-Deuterium Exchange Mass Spectrometry: Challenges and Outlook.Frontiers in immunology · 2022Review
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Computational approaches to therapeutic antibody design: established methods and emerging trends.Briefings in bioinformatics · 2020Review
- Epitope mapping of diverse influenza Hemagglutinin drug candidates using HDX-MS.Scientific reports · 2019Article
- Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.Antibodies (Basel, Switzerland) · 2018Review
- Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
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- High Resolution Mapping of Bactericidal Monoclonal Antibody Binding Epitopes on Staphylococcus aureus Antigen MntC.PLoS pathogens · 2016Article
- Engineering less immunogenic and antigenic FVIII proteins.Cellular immunology · 2016Review
- Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.Scientific reports · 2015Article
- Applications of hydrogen/deuterium exchange MS from 2012 to 2014.Analytical chemistry · 2015Review
- Six amino acid residues in a 1200 Å2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.PloS one · 2015Article
- Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors.Journal of thrombosis and haemostasis : JTH · 2015Article
- HDX-MS guided drug discovery: small molecules and biopharmaceuticals.Current opinion in structural biology · 2014Review
- Current approaches to fine mapping of antigen-antibody interactions.Immunology · 2014Review
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Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe development of anti-factor VIII antibodies (inhibitors) is a significant complication in the management of patients with hemophilia A, leading to significant increases in morbidity and treatment cost. Using a panel of mAbs against different epitopes on FVIII, we have recently shown that epitope specificity, inhibitor kinetics and time to maximum inhibition are more important than inhibitor titer in predicting responses to FVIII and the combination of FVIII and recombinant FVIIa. In particular, a subset of high-titer inhibitors responded to high-dose FVIII, which would not be predicted on the basis of their inhibitor titer alone. Thus, the ability to quickly map the epitope spectrum of patient plasma with a clinically feasible assay may fundamentally change how clinicians approach the treatment of high-titer inhibitor patients.
objectivesTo map the epitopes of anti-FVIII mAbs, three of which are classic inhibitors and one of which is a non-classic inhibitor, by the use of hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS).
methodsThe binding epitopes of four mAbs targeting the FVIII C2 domain were mapped with HDX-MS.
resultsThe epitopes determined with HDX-MS are consistent with those obtained earlier through structural characterization and antibody competition assays. In addition, classic and non-classic inhibitor epitopes could be distinguished by the use of a limited subset of C2 domain-derived peptic fragments.
conclusionOur results demonstrate the effectiveness and robustness of the HDX-MS method for epitope mapping, and suggest a potential role of rapid mapping of FVIII inhibitor epitopes in facilitating individualized treatment of inhibitor patients.
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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.