Structural modification of DNA--a therapeutic option in SLE?
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.
Department of Clinical Research, University Hospital Bern, Murtenstrasse 50, P. O. Box 44, CH-3010 Bern, Switzerland (). The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA ().
Steffen
S
Frese
Department of Clinical Research, University Hospital Bern, Murtenstrasse 50, P. O. Box 44, CH-3010 Bern, Switzerland (). The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA ().
Betty
B
Diamond
D000818:Animals; D004247:DNA / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D004247:DNA