Brief Report: Dystrophin Immunity in Duchenne's Muscular Dystrophy.

被引：455

作者：

Mendell, Jerry R. ^{[2
,3
]}

Campbell, Katherine ^{[1
,3
]}

Rodino-Klapac, Louise ^{[2
,3
]}

Sahenk, Zarife ^{[2
,3
]}

Shilling, Chris ^{[2
]}

Lewis, Sarah ^{[2
]}

Bowles, Dawn ^{[4
]}

Gray, Steven ^{[4
]}

Li, Chengwen ^{[4
]}

Galloway, Gloria ^{[2
]}

Malik, Vinod ^{[2
]}

Coley, Brian ^{[2
]}

Clark, K. Reed ^{[2
]}

Li, Juan ^{[5
]}

Xiao, Xiao ^{[5
]}

Samulski, Jade ^{[6
]}

McPhee, Scott W. ^{[6
]}

Samulski, R. Jude ^{[4
]}

Walker, Christopher M. ^{[1
,3
]}

机构：

[1] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Res Inst, Columbus, OH 43205 USA

[2] Nationwide Childrens Hosp, Ctr Gene Therapy, Res Inst, Columbus, OH 43205 USA

[3] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA

[4] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA

[5] Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC USA

[6] Asklepios BioPharmaceut, Chapel Hill, NC USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 15期

关键词：

GENE-TRANSFER; CONGENITAL AMAUROSIS; MUSCLE; REARRANGEMENTS; DEGENERATION; RESPONSES; THERAPY; HUMANS; TRIAL; MICE;

D O I：

10.1056/NEJMoa1000228

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.).

引用

页码：1429 / 1437

页数：9

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