VP.24 T Cell-mediated immune response to dystrophin in Duchenne muscular dystrophy - A natural history study

Abstract

Duchenne muscular dystrophy is caused by a lack of dystrophin. Several strategies exist to restore dystrophin production, including exon skipping and gene therapy. However, dystrophin epitopes, expressed in revertant fibres in non-treated patients, may elicit a T cell-mediated immune response, which could reduce the efficacy of therapies designed to restore dystrophin. We performed enzyme-linked immunospot interferon-gamma assays on peripheral blood mononuclear cells from 78 paediatric patients with DMD from a natural history study. Immune responses to dystrophin were quantified using 368 peptides spanning the entire protein, organized into nine pools. Peptide mapping pools were used to further localize the immune response in one positive patient. Overall, our results show that pre-existing T cell responses to dystrophin are uncommon (8%), inconsistent and low-level. Whilst this does provide some confidence for dystrophin restorative treatments, the fact that some patients are responsive warrants that individuals be screened prior to treatment.