Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII covalent states.

ABSTRACT:

Abstract

Hemophilia A is a chronic life-threatening condition caused by the deficiency or dysfunction of plasma coagulation factor VIII (FVIII) and commonly managed by prophylaxis with regular infusion of FVIII protein. A major obstacle to FVIII replacement therapy is the generation of alloantibodies that diminish efficacy. Disulfide bonds link pairs of cysteine residues in proteins and, in several proteins, have been found to be only partially formed in the mature proteins. FVIII contains 8 disulfide bonds and their redox state in human blood and recombinant FVIII was determined using differential cysteine alkylation and mass spectrometry. All 8 disulfide bonds were found to be unformed in ∼10% to ∼70% of molecules of FVIII populations, which suggested a conformational flexibility

SUBMITTER: Butera D 

PROVIDER: S-EPMC12305225 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature