Intramuscular plasmid DNA injection can accelerate autoimmune responses.
We have investigated if the administration of plasmid vectors engineered for gene delivery into mammalian muscle induced the production of anti-double stranded (ds) DNA and anti-nuclear autoantibodies in normal and autoimmunity-prone mouse models. In normal mice, repeated injection of plasmid DNA did not trigger an anti-DNA response. The presence of eukaryotic transcription factor binding sites in plasmid vectors did not increase autoantibody formation in these animals. In contrast, repeated injection of such plasmids in autoimmunity-prone MRL/MpJ mice caused a significant increase in both anti-dsDNA and anti-nuclear antibody levels. Thus the repeated administration of bacterial plasmids containing eukaryotic promoter elements may induce immune responses with generation of antibodies cross-reacting not only with the mammalian DNA, but also with nuclear antigens. The potential for iatrogenic autoimmunity in susceptible individuals should be considered.
MacColl
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Department of Medicine, Royal Free and University College Medical School, London, UK.
Bunn
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C
Goldspink
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Bouloux
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P
Górecki
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DC
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000917:Antibody Formation; D015551:Autoimmunity; D004247:DNA / Q000008:administration & dosage*; D019084:Fluorescent Antibody Technique, Indirect; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000009:adverse effects*; D007273:Injections, Intramuscular; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal
D000974:Antibodies, Antinuclear; D004247:DNA