Toggle Main Menu Toggle Search

Open Access padlockePrints

T Cell Responses to Dystrophin in a Natural History Study of Duchenne Muscular Dystrophy

Lookup NU author(s): Professor Volker StraubORCiD, Professor Michela GuglieriORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, but many patients have rare revertant fibers that express dystrophin. The skeletal muscle pathology of DMD patients includes immune cell infiltration and inflammatory cascades. There are several strategies to restore dystrophin in skeletal muscles of patients, including exon skipping and gene therapy. There is some evidence that dystrophin restoration leads to a reduction in immune cells, but dystrophin epitopes expressed in revertant fibers or following genome editing, cell therapy, or microdystrophin delivery after adeno-associated viral gene therapy may elicit T cell production in patients. This may affect the efficacy of the therapeutic intervention, and potentially lead to serious adverse events. To confirm and extend previous studies, we performed annual enzyme- linked immunospot interferon-gamma assays on peripheral blood mononuclear cells from 77 pediatric boys with DMD recruited into a natural history study, 69 of whom (89.6%) were treated with corticosteroids. T cell responses to dystrophin were quantified using a total of 368 peptides spanning the entire dystrophin protein, organized into nine peptide pools. Peptide mapping pools were used to further localize the immune response in one positive patient. Six (7.8%) patients had a T cell-mediated immune response to dystrophin at at least one time point. All patients who had a positive result had been treated with corticosteroids, either prednisolone or prednisone. Our results show that ∼8% of DMD individuals in our cohort have a pre-existing T cell-mediated immune response to dystrophin, despite steroid treatment. Although these responses are relatively low level, this information should be considered a useful immunological baseline before undertaking clinical trials and future DMD studies. We further highlight the importance for a robust, reproducible standard operating procedure for collecting, storing, and shipping samples from multiple centers to minimize the number of inconclusive data.

Publication metadata

Author(s): Anthony K, Ala P, Catapano F, Meng J, Domingos J, Perry M, Ricotti V, Maresh K, Phillips LC, Servais L, Seferian AM, De Lucia S, de Groot I, Krom YD, Verschuuren JGM, Niks EH, Straub V, Guglieri M, Voit T, Morgan J, Muntoni F

Publication type: Article

Publication status: Published

Journal: Human Gene Therapy

Year: 2023

Volume: 34

Issue: 9-10

Pages: 439-448

Print publication date: 17/05/2023

Online publication date: 01/12/2022

Acceptance date: 02/04/2018

ISSN (print): 1043-0342

ISSN (electronic): 1557-7422

Publisher: Mary Ann Liebert, Inc.


DOI: 10.1089/hum.2022.166

PubMed id: 36453228


Altmetrics provided by Altmetric