ArticleBlood2017
Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Acquired hemophilia A: an illustrated review based on the French National Guidelines.Research and practice in thrombosis and haemostasis · 2026Review
- A combinatorial CAAR-T cell strategy to eliminate factor VIII inhibitors in preclinical models of hemophilia A.iScience · 2026Article
- Profiling of Anti-FVIII Antibodies in Acquired Haemophilia A: 'Insights into Domain Specificity, Isotype Variability, and Clinical Correlations'.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Factor VIII Antibodies Demonstrate Type I or Type II Kinetics in Acquired Haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 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
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain.Journal of thrombosis and haemostasis : JTH · 2024Article
- Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside.Current issues in molecular biology · 2024Review
- Immunotherapy of acquired hemophilia A.Hematology. American Society of Hematology. Education Program · 2023Article
- Targets of autoantibodies in acquired hemophilia A are not restricted to factor VIII: data from the GTH-AH 01/2010 study.Blood advances · 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
- Measurement of coagulation factor antibody levels is useful for diagnosis and determining therapeutic efficacy in hemorrhagic patients with autoantibodies to coagulation factor VIII and factor V: results from a single center in Japan.International journal of hematology · 2022Article
- Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor.Blood · 2021Article
- Article
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Acquired Haemophilia A: An Intriguing Disease.Mediterranean journal of hematology and infectious diseases · 2020Review
- Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.Antibodies (Basel, Switzerland) · 2018Review
- Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review.Haemophilia : the official journal of the World Federation of Hemophilia · 2018Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. The analysis with HSA-fVIII domain proteins confirmed the results of the HSM approach but resulted in higher detection levels. The higher detection levels with HSA-fVIII domain proteins are a result of antibody cross-reactivity with human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-, and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63). Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed overlapping epitopes with murine C1-specific group A mAbs including 2A9. Mutational analyses identified distinct crucial binding residues for LE2E9 (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies was particularly observed in patients with AHA. Overall, our study demonstrates that the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral anti-fVIII immune response in acquired and congenital hemophilia inhibitor patients.
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