title: DNA-damaging autoantibodies and cancer: the lupus butterfly theory.
abstract: Autoantibodies reactive against host DNA are detectable in the circulation of most people with systemic lupus erythematosus (SLE). The long-held view that antibodies cannot penetrate live cells has been disproved. A subset of lupus autoantibodies penetrate cells, translocate to nuclei, and inhibit DNA repair or directly damages DNA. The result of these effects depends on the microenvironment and genetic traits of the cell. Some DNA-damaging antibodies alone have little impact on normal cells, but in the presence of other conditions, such as pre-existing DNA-repair defects, can become highly toxic. These findings raise new questions about autoimmunity and DNA damage, and reveal opportunities for new targeted therapies against malignancies particularly vulnerable to DNA damage. In this Perspectives article, we review the known associations between SLE, DNA damage and cancer, and propose a theory for the effects of DNA-damaging autoantibodies on SLE pathophysiology and cancer risk.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, 15 York Street, New Haven, Connecticut 06520, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Noble
authors.affiliation: Department of Medicine, Divisions of Rheumatology and Clinical Epidemiology, McGill University, 687 Avenue des Pins Quest, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Bernatsky
authors.affiliation: Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Clarke
authors.affiliation: Centre for Rheumatology, Department of Medicine, Rayne Building, 5 University Street, University College London, London WC1E 6JF, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, Illinois 60611, USA.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, 15 York Street, New Haven, Connecticut 06520, USA.|Yale Cancer Center, Yale School of Medicine, 15 York Street, New Haven, Connecticut 06520, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hansen
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers