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Structural modification of DNA—a therapeutic option in SLE?

Nature Reviews Rheumatology volume 7, pages 733738 (2011) | Download Citation

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, with glomerulonephritis representing a frequent and serious manifestation. SLE is characterized by the presence of various autoantibodies, including anti-DNA antibodies that occur in approximately 70% of patients with SLE and which contribute to disease pathogenesis. Consequently, immunosuppressive therapies are applied in the treatment of SLE to reduce autoantibody levels. However, increasing evidence suggests that DNA—especially double-stranded DNA—constitutes an important pathogenic factor that is able to activate inflammatory responses by itself in autoimmune diseases. Therefore, modifying the structure of DNA to reduce its pathogenicity might be a more targeted approach for the treatment of SLE than immunosuppression. This article presents information in support of this strategy, and discusses the potential methods of DNA structure manipulation—in light of data obtained from mouse models of SLE—including topoisomerase I inhibition, administration of DNase I, or modification of histones using heparin or histone deacetylase inhibitors.

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Author information

Affiliations

  1. Department of Clinical Research, University Hospital Bern, Murtenstrasse 50, P. O. Box 44, CH-3010 Bern, Switzerland

    • Steffen Frese
  2. The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA

    • Betty Diamond

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Contributions

S. Frese researched the data for the article and wrote the article. B. Diamond contributed to review and/or editing of the manuscript before submission. S. Frese and B. Diamond contributed equally to discussions of the content.

Competing interests

S. Frese has filed a patent with the European Patent Office for the treatment of autoimmune diseases by use of topoisomerase I inhibitors. B. Diamond declares no competing interests.

Corresponding author

Correspondence to Steffen Frese.

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DOI

https://doi.org/10.1038/nrrheum.2011.153

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