Dystrophin immunity in Duchenne's muscular dystrophy.
Dystrophin immunity in Duchenne's muscular dystrophy.
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DOI：
10.1056/nejmoa1000228
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发表时间：
2010-10-07
期刊：
影响因子：
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通讯作者：
Walker CM
中科院分区：
文献类型：
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作者：
Mendell JR;Campbell K;Rodino-Klapac L;Sahenk Z;Shilling C;Lewis S;Bowles D;Gray S;Li C;Galloway G;Malik V;Coley B;Clark KR;Li J;Xiao X;Samulski J;McPhee SW;Samulski RJ;Walker CM
我们报告了6例Duchenne肌营养不良症患者将功能性肌营养不良基因转移到骨骼肌。治疗后检测到抗肌萎缩蛋白特异的T细胞，即使在骨骼肌中没有看到功能蛋白的情况下，也提供了转基因表达的证据。在载体治疗前，在两名患者中意外检测到循环中的营养不良蛋白特异性T细胞。反式抗肌营养不良蛋白纤维在自发的框内剪接后，从缺失的内源性基因表达功能性截断的抗肌营养不良蛋白，含有自身反应性T细胞靶向的表位。在设计和监测这种疾病的实验治疗方法时，应考虑T细胞对自身和非自身抗肌营养不良蛋白表位免疫的可能性。(由肌营养不良协会和其他机构资助；ClinicalTrials.gov编号，NCT00428935。)
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.)