Differential impacts of ectopic N-glycosylation on FVIII folding trafficking and activity which highlight complex disease-causing mechanisms of FVIII missense mutations.
The type of F8 mutation is the main predictor of inhibitor development in patients with severe hemophilia A. Findings confirm an association between the synthesis of minute amounts of FVIII and inhibitor protection.
Human FVIII gene transfer without in vivo selection of manipulated cells can introduce immune tolerance in hemophilia A mice and this immune tolerance is CD4(+) T cell mediated.
the existing epidemiologic investigations with an overview of the range of possible biochemical and immunologic mechanisms that may contribute to the different immune outcomes observed with plasma-derived and recombinant FVIII products.
our results demonstrate that the N-glycosylation sequon in the A2 domain is located in a structural element that is critically required for proper folding and conformation of FVIII.
Each hFVIII vector was administered to FVIII knockout (KO) mice at a dose of 10(10) genome copies (GC) per mouse. Criteria for distinguishing the performance of the different enhancer/promoter combinations were established prior to the initiation of the studies.
the results indicate that residues in the C1 and/or C2 domains of factor VIII are implicated in immunogenic factor VIII uptake at least in vitro Conversely in vivo the binding to endogenous von Willebrand factor masks the reducing effect of mutations in the C domains on factor VIII immunogenicity.
In this meta-analysis we have assessed the association between the FXIII-A Val34Leu polymorphism and intracerebral hemorrhage risk. The results of a combined analysis showed no significant association between the FXIII-A Val34Leu polymorphism and ICH risk in the overall population. The results of this meta-analysis suggest that the FXIII-A Val34Leu polymorphism is not associated with ICH risk in a Caucasian population.
Platelet-targeted FVIII gene therapy has higher therapeutic efficacy compared to factor VIII replacement therapy may be due to accelerated thrombin generation.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.