TY - JOUR
T1 - Dystrophin immunity in Duchenne's muscular dystrophy
AU - Mendell, Jerry R.
AU - Campbell, Katherine
AU - Rodino-Klapac, Louise
AU - Sahenk, Zarife
AU - Shilling, Chris
AU - Lewis, Sarah
AU - Bowles, Dawn
AU - Gray, Steven
AU - Li, Chengwen
AU - Galloway, Gloria
AU - Malik, Vinod
AU - Coley, Brian
AU - Clark, K. Reed
AU - Li, Juan
AU - Xiao, Xiao
AU - Samulski, Jade
AU - McPhee, Scott W.
AU - Samulski, R. Jude
AU - Walker, Christopher M.
PY - 2010/10/7
Y1 - 2010/10/7
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa1000228
DO - 10.1056/NEJMoa1000228
M3 - Article
C2 - 20925545
AN - SCOPUS:77957725001
SN - 0028-4793
VL - 363
SP - 1429
EP - 1437
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 15
ER -