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Intramuscular plasmid DNA injection can accelerate autoimmune responses

Gene Therapy volume 8, pages 1354–1356 (2001)Cite this article

Abstract

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.

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References

  1. Gurunathan S, Klinman DM, Seder RA . DNA vaccines: immunology, application, and optimization Annu Rev Immunol 2000 18: 927–974

    Article  CAS  Google Scholar 

  2. MacColl GS, Goldspink G, Bouloux PMG . Using skeletal muscle as an artificial endocrine tissue J Endocrinol 1999 162: 1–9

    Article  CAS  Google Scholar 

  3. Parker SE et al. Plasmid DNA malaria vaccine: tissue distribution and safety studies in mice and rabbits Hum Gene Ther 1999 10: 741–758

    Article  CAS  Google Scholar 

  4. Górecki DC, Simons JP . The dangers of DNA vaccination Nat Med 1999 5: 126

    Article  Google Scholar 

  5. Pisetsky DS . Immunostimulatory DNA: a clear and present danger? Nat Med 1997 3: 829–831

    Article  CAS  Google Scholar 

  6. Stacey KJ, Sweet MJ, Hume DA . Macrophages ingest and are activated by bacterial DNA J Immunol 1996 157: 2116–2122

    CAS  Google Scholar 

  7. 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

    Article  CAS  Google Scholar 

  8. 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

    Article  CAS  Google Scholar 

  9. Jackson mouse database 2000 http://jaxmice.jax.org/index.shtml

  10. 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

    Article  CAS  Google Scholar 

  11. Jiao S et al. Direct gene transfer into nonhuman primate myofibers in vivo Hum Gene Ther 1992 3: 21–33

    Article  CAS  Google Scholar 

  12. Katsumi A et al. Humoral and cellular immunity to an encoded protein induced by direct DNA injection Hum Gene Ther 1994 5: 1335–1339

    Article  CAS  Google Scholar 

  13. Mor G et al. Do DNA vaccines induce autoimmune disease? Hum Gene Ther 1997 8: 293–300

    Article  CAS  Google Scholar 

  14. 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

    CAS  PubMed  Google Scholar 

  15. 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

    Article  CAS  Google Scholar 

  16. Devlam K et al. Detection and identification of antinuclear autoantibodies in the serum of normal blood-donors Clin Exp Rheumatol 1993 11: 393–397

    CAS  Google Scholar 

  17. Tan EM et al. Range of antinuclear antibodies in ‘healthy’ individuals Arthr Rheum 1997 40: 1601–1611

    Article  CAS  Google Scholar 

  18. 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

    CAS  PubMed  Google Scholar 

  19. Rosenberg AM et al. Prevalence of antinuclear antibodies in a rural population J Toxicol Environ Health A 1999 57: 225–236

    Article  CAS  Google Scholar 

  20. Eilat D, Naparstek Y . Anti-DNA autoantibodies: a puzzle of autoimmune phenomena Immunol Today 1999 20: 339–342

    Article  CAS  Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

  22. 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

    Article  CAS  Google Scholar 

  23. 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

    Article  CAS  Google Scholar 

  24. Tsunoda I et al. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA Brain Pathol 1999 9: 481–493

    Article  CAS  Google Scholar 

  25. 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

    Article  CAS  Google Scholar 

  26. 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

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Royal Free and University College Medical School, London, UK

    G MacColl & P Bouloux

  2. Department of Clinical Immunology, Royal Free and University College Medical School, London, UK

    C Bunn

  3. Department of Anatomy and Developmental Biology, Royal Free and University College Medical School, London, UK

    G Goldspink & DC Górecki

Authors
  1. G MacColl
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  2. C Bunn
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  3. G Goldspink
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  4. P Bouloux
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  5. DC Górecki
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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

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