Factor VIII cross-matches to the human proteome reduce the predicted inhibitor risk in missense mutation hemophilia A.

ABSTRACT: Single missense mutations in the F8 gene encoding the coagulation protein factor VIII give rise predominantly to non-severe hemophilia A. Despite only a single amino acid sequence difference between the replacement, therapeutic factor VIII and the patient's endogenous factor VIII, therapeutic factor VIII may still be perceived as foreign by the recipient's immune system and trigger an immune response (inhibitor). Inhibitor formation is a life-long risk for patients with non-severe hemophilia A treated with therapeutic factor VIII, but remains difficult to predict. The aim of this study was to understand whether fortuitous, primary sequence cross-matches between therapeutic factor VIII and proteins in the human proteome are the reason why certain F8 mutations are not associate

SUBMITTER: Hart DP 

PROVIDER: S-EPMC6395325 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature