ArticleHaematologica2018
N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
Article in Haematologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The contribution of the sinusoidal endothelial cell receptors CLEC4M, stabilin-2, and SCARA5 to VWF-FVIII clearance in thrombosis and hemostasis.Journal of thrombosis and haemostasis : JTH · 2023Pooled it
- Decoding full-length factor VIII through the structural and functional lens of its B domain.Blood vessels, thrombosis & hemostasis · 2026Article
- Impact of Inhibitor Development on the Cost Effectiveness of Prophylactic Treatment with Recombinant Factor VIII in Previously Untreated Patients with Severe Hemophilia A.PharmacoEconomics - open · 2026Article
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- Mice possess a more limited natural antihuman factor VIII antibody repertoire than humans that is produced disproportionately by marginal zone B cells.Journal of thrombosis and haemostasis : JTH · 2024Article
- The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A.Frontiers in immunology · 2024Article
- Anti-FVIII antibodies in Black and White hemophilia A subjects: do F8 haplotypes play a role?Blood advances · 2023Article
- Influence of N-glycosylation in the A and C domains on the immunogenicity of factor VIII.Blood advances · 2022Article
- An etanercept O-glycovariant with enhanced potency.Molecular therapy. Methods & clinical development · 2022Article
- Nonhuman sugars cause factor VIII troubles.Blood · 2022Article
- Article
- Removal of single-site N-linked glycans on factor VIII alters binding of domain-specific monoclonal antibodies.Journal of thrombosis and haemostasis : JTH · 2022Article
- Combination ofJournal of clinical medicine · 2022Article
- H11-induced immunoprotection is predominantly linked to N-glycan moieties duringFrontiers in immunology · 2022Article
- Comprehensive N- and O-glycosylation mapping of human coagulation factor V.Journal of thrombosis and haemostasis : JTH · 2020Article
- Immune Responses to Plasma-Derived Versus Recombinant FVIII Products.Frontiers in immunology · 2020Review
- Comparative glycosylation mapping of plasma-derived and recombinant human factor VIII.PloS one · 2020Article
- The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.Journal of thrombosis and haemostasis : JTH · 2019Article
- Molecular Aggregation of Marketed Recombinant FVIII Products: Biochemical Evidence and Functional Effects.TH open : companion journal to thrombosis and haemostasis · 2019Article
- Tolerating Factor VIII: Recent Progress.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells. Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared to Chinese hamster ovary cell-derived factor VIII. Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor. Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites. Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression. We did, however, observe increased levels of immunoglobulin M specific to baby hamster kidney-derived factor VIII in naïve hemophilia A mice. De-N-glycosylation enhanced immunoglobulin M binding, suggesting that N-glycan occupancy masks epitopes. Elevated levels of immunoglobulin M and immunoglobulin G specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased immunoglobulin G binding. Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of immunoglobulin M- and immunoglobulin G-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
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