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.
Your institute does not have access to this article
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Gurunathan S, Klinman DM, Seder RA . DNA vaccines: immunology, application, and optimization Annu Rev Immunol 2000 18: 927–974
MacColl GS, Goldspink G, Bouloux PMG . Using skeletal muscle as an artificial endocrine tissue J Endocrinol 1999 162: 1–9
Parker SE et al. Plasmid DNA malaria vaccine: tissue distribution and safety studies in mice and rabbits Hum Gene Ther 1999 10: 741–758
Górecki DC, Simons JP . The dangers of DNA vaccination Nat Med 1999 5: 126
Pisetsky DS . Immunostimulatory DNA: a clear and present danger? Nat Med 1997 3: 829–831
Stacey KJ, Sweet MJ, Hume DA . Macrophages ingest and are activated by bacterial DNA J Immunol 1996 157: 2116–2122
Wells KE et al. Immune responses, not promoter inactivation, are responsible for decreased long-term expression following plasmid gene transfer into skeletal muscle FEBS Lett 1997 407: 164–168
Davis HL, McCluskie MJ, Gerin JL, Purcell RH . DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines Proc Natl Acad Sci USA 1996 93: 7213–7218
Jackson mouse database 2000 http://jaxmice.jax.org/index.shtml
Sedegah M, Hedstrom R, Hobart P, Hoffman SL . Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein Proc Natl Acad Sci USA 1994 91: 9866–9870
Jiao S et al. Direct gene transfer into nonhuman primate myofibers in vivo Hum Gene Ther 1992 3: 21–33
Katsumi A et al. Humoral and cellular immunity to an encoded protein induced by direct DNA injection Hum Gene Ther 1994 5: 1335–1339
Mor G et al. Do DNA vaccines induce autoimmune disease? Hum Gene Ther 1997 8: 293–300
Karounos DG, Grudier JP, Pisetsky DS . Spontaneous expression of antibodies to DNA of various species origin in sera of normal subjects and patients with systemic lupus erythematosus J Immunol 1988 140: 451–455
Wu ZQ, Drayton D, Pisetsky DS . Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE) Clin Exp Immunol 1997 109: 27–31
Devlam K et al. Detection and identification of antinuclear autoantibodies in the serum of normal blood-donors Clin Exp Rheumatol 1993 11: 393–397
Tan EM et al. Range of antinuclear antibodies in ‘healthy’ individuals Arthr Rheum 1997 40: 1601–1611
Zarmbinski MA, Messner RP, Mandel JS . Anti-dsDNA antibodies in laboratory workers handling blood from patients with systemic lupus erythematosus J Rheumatol 1992 19: 1380–1384
Rosenberg AM et al. Prevalence of antinuclear antibodies in a rural population J Toxicol Environ Health A 1999 57: 225–236
Eilat D, Naparstek Y . Anti-DNA autoantibodies: a puzzle of autoimmune phenomena Immunol Today 1999 20: 339–342
Kaliyaperumal A, Mohan C, Wu W, Datta SK . Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus J Exp Med 1996 183: 2459–2469
Moens U et al. In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones Proc Natl Acad Sci USA 1995 92: 12393–12397
Williamson RA et al. Ant-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis Proc Natl Acad Sci USA 2001 98: 1793–1798
Tsunoda I et al. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA Brain Pathol 1999 9: 481–493
Novo FJ, Górecki DC, Goldspink G, MacDermot KD . Gene transfer and expression of human alpha-galactosidase from mouse muscle in vitro and in vivo Gene Therapy 1997 4: 488–492
Humbel RL . Detection of antinuclear antibodies by immunofluorescence In: Van Vendrooij WJ, Maini RN (eds) Manual of Biological Markers of Disease: Methods of Autoantibody Detection Kluwer Academic Publishers: London 1993 pp A2.1–A2.16
About this article
Cite this article
MacColl, G., Bunn, C., Goldspink, G. et al. Intramuscular plasmid DNA injection can accelerate autoimmune responses. Gene Ther 8, 1354–1356 (2001). https://doi.org/10.1038/sj.gt.3301537
- plasmid vector
- anti-DNA antibodies
- anti-nuclear antibodies
Hybrid polymeric-protein nano-carriers (HPPNC) for targeted delivery of TGFβ inhibitors to hepatocellular carcinoma cells
Journal of Materials Science: Materials in Medicine (2017)
Gene Therapy (2003)