Autoimmune anemia in macaques following erythropoietin gene therapy
Autoimmune anemia in macaques following erythropoietin gene therapy
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DOI：
10.1182/blood-2003-11-3845
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发表时间：
2004-05-01
期刊：
影响因子：
20.3
通讯作者：
Moullier, P
中科院分区：
文献类型：
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作者：
Chenuaud, P;Larcher, T;Moullier, P
我们通过重组腺相关病毒在9只食蟹猴的骨骼肌中递送了由强力霉素调控的启动子驱动的同源促红细胞生成素（Epo）cDNA。在诱导后，获得快速的超生理水平的Epo。出乎意料的是，一些个体发展出与针对内源性Epo的中和抗体的出现相关的严重贫血。内源性促红细胞生成素和载体序列都是相同的。这是灵长类动物中由于表达自身抗原的基因的基因转移而意外发展为自身免疫性疾病的第一个例子。当治疗性蛋白质从异位部位以高水平产生时，引起了一些关注。（C）2004年由美国血液学学会。
We delivered the homologous erythropoietin (Epo) cDNA driven from a doxycycline-regulated promoter via recombinant adeno-associated virus in skeletal muscle of 9 cynomolgus macaques. Upon induction, rapid supraphysiologic levels of Epo were obtained. Unexpectedly, some individuals developed a profound anemia that correlated with the appearance of neutralizing antibodies against the endogenous Epo. Both the endogenous erythropoietin and vector sequences were identical. This is the first example of the inadvertent development of an autoimmune disease in primates as a result of gene transfer of a gene expressing a self-antigen. It raises some concerns when a therapeutic protein is produced at high levels from an ectopic site. (C)2004 by The American Society of Hematology.