ArticleBlood2012
Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A mice.
Article in Blood, 2012. 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
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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
23 citing papers in PubMed, 40 citations in OpenAlex.
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides.Haematologica · 2025Article
- Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension.Haematologica · 2025Article
- 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
- Structure of coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor.Blood · 2023Article
- Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner.Frontiers in immunology · 2023Article
- Isolated Variable Domains of an Antibody Can Assemble on Blood Coagulation Factor VIII into a Functional Fv-like Complex.International journal of molecular sciences · 2022Article
- Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations.Journal of nanobiotechnology · 2021Article
- Structure of blood coagulation factor VIII in complex with an anti-C1 domain pathogenic antibody inhibitor.Blood · 2021Article
- Article
- Molecular Mechanisms of Inhibitor Development in Hemophilia.Mediterranean journal of hematology and infectious diseases · 2020Review
- Removal of Mannose-Ending Glycan at AsnFrontiers in immunology · 2020Article
- Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A.Haematologica · 2019Article
- Tolerating Factor VIII: Recent Progress.Frontiers in immunology · 2019Review
- Complement C3 is a novel modulator of the anti-factor VIII immune response.Haematologica · 2018Article
- The C1 and C2 domains of blood coagulation factor VIII mediate its endocytosis by dendritic cells.Haematologica · 2017Article
- Article
- von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII.Haematologica · 2016Article
- Article
- Factor VIII C1 domain spikes 2092-2093 and 2158-2159 comprise regions that modulate cofactor function and cellular uptake.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Development of neutralizing Abs to blood coagulation factor VIII (FVIII) provides a major complication in hemophilia care. In this study we explored whether modulation of the uptake of FVIII by APCs can reduce its intrinsic immunogenicity. Endocytosis of FVIII by professional APCs is significantly blocked by mAb KM33, directed toward the C1 domain of FVIII. We created a C1 domain variant (FVIII-R2090A/K2092A/F2093A), which showed only minimal binding to KM33 and retained its activity as measured by chromogenic assay. FVIII-R2090A/K2092A/F2093A displayed a strongly reduced internalization by human monocyte-derived dendritic cells and macrophages, as well as murine BM-derived dendritic cells. We subsequently investigated the ability of this variant to induce an immune response in FVIII-deficient mice. We show that mice treated with FVIII-R2090A/K2092A/F2093A have significantly lower anti-FVIII Ab titers and FVIII-specific CD4(+) T-cell responses compared with mice treated with wild-type FVIII. These data show that alanine substitutions at positions 2090, 2092, and 2093 reduce the immunogenicity of FVIII. According to our findings we hypothesize that FVIII variants displaying a reduced uptake by APCs provide a novel therapeutic approach to reduce inhibitor development in hemophilia A.
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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.