Hemophilia A subjects with an intron-22 gene inversion mutation show CD4⁺ T-effector responses to multiple epitopes in FVIII.

ABSTRACT:

Background

Almost half of severe hemophilia A (HA) is caused by an intron 22 inversion mutation (Int22Inv), which disrupts the 26-exon F8 gene. Inverted F8 mRNA exons 1-22 are transcribed, while F8B mRNA, containing F8 exons 23-26, is transcribed from a promoter within intron 22. Neither FVIII activity nor FVIII antigen (cross-reacting material, CRM) are detectable in plasma of patients with an intron-22 inversion.

Objectives

To test the hypothesis that (putative) intracellular synthesis of FVIII proteins encoded by inverted F8 and F8B mRNAs confers T-cell tolerance to almost the entire FVIII sequence, and to evaluate the immunogenicity of the region encoded by the F8 exon 22-23 junction sequence.

Patients/methods

Perip

SUBMITTER: Gunasekera D 

PROVIDER: S-EPMC10015889 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature