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 Blood, 1 May 2004, Vol. 103, No. 9, pp. 3303-3304.
Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-11-3845.

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Submitted November 12, 2003
Accepted December 16, 2003

Autoimmune Anemia in Macaques Following Erythropoietin Gene Therapy

Pierre Chenuaud, Thibaut Larchet, Joseph E Rabinowitz, Nathalie Provost, Yan Cherel, Nicole Casadevall, R J Samulski, and Philippe Moullier*

INSERM ERM 01-05, Centre Hospitalo-Universitaire, Nantes, France
Gene Therapy, University of North Carolina, Chapel Hill, NC, USA
INRA UR 703, Ecole Nationale Veterinaire, Nantes, France
Service d'Hematologie Biologique, CHU Hotel-Dieu, Paris, France

* Corresponding author; email: moullier{at}sante.univ-nantes.fr.

We delivered the homologous erythropoietin 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 which 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.


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