Autoimmune anemia in macaques following erythropoietin gene therapy

被引：94

作者：

Chenuaud, P

Larcher, T

Rabinowitz, JE

Provost, N

Cherel, Y

Casadevall, N

Samulski, RJ

Moullier, P

机构：

[1] INSERM, Nantes, France

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

[3] Ecole Natl Vet, Nantes, France

[4] Serv Hematol Biol, Paris, France

来源：

BLOOD | 2004年 / 103卷 / 09期

关键词：

D O I：

10.1182/blood-2003-11-3845

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

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收藏

页码：3303 / 3304

页数：2

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