T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site.

ABSTRACT:

Background

Development of neutralizing anti-factor (F)VIII antibodies ('inhibitors') is a serious clinical problem in hemophilia A. Increased inhibitor risk has been associated with certain FVIII missense substitutions, including R593C in the A2 domain.

Objectives

The aim of the present study was to identify T-cell epitopes in FVIII and characterize T-cell responses in two unrelated hemophilia A subjects sharing F8-R593C and HLA-DRB1*1101 genotypes. We hypothesized that the hemophilic substitution site coincides with an important T-cell epitope.

Patients/methods

The binding affinities of peptides for recombinant HLA-DR proteins were measured and compared with epitope prediction results. CD4+ T cells were stimulated using peptides and stained with fluorescent, peptide-

SUBMITTER: James EA 

PROVIDER: S-EPMC4323178 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature