Dystrophin immunity in Duchenne's muscular dystrophy.
We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne's muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.).
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Related Subject Headings
- Transgenes
- T-Lymphocytes
- Protein Biosynthesis
- Muscular Dystrophy, Duchenne
- Muscle, Skeletal
- Male
- Immunity, Cellular
- Humans
- Genetic Vectors
- Genetic Therapy
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transgenes
- T-Lymphocytes
- Protein Biosynthesis
- Muscular Dystrophy, Duchenne
- Muscle, Skeletal
- Male
- Immunity, Cellular
- Humans
- Genetic Vectors
- Genetic Therapy