DNA-damaging autoantibodies and cancer: The lupus butterfly theory

Philip W. Noble, Sasha Bernatsky, Ann E. Clarke, David A. Isenberg, Rosalind Ramsey-Goldman, James E. Hansen*

*Corresponding author for this work

Research output: Contribution to journalReview article

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)429-434
Number of pages6
JournalNature Reviews Rheumatology
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Rheumatology

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    Noble, P. W., Bernatsky, S., Clarke, A. E., Isenberg, D. A., Ramsey-Goldman, R., & Hansen, J. E. (2016). DNA-damaging autoantibodies and cancer: The lupus butterfly theory. Nature Reviews Rheumatology, 12(7), 429-434. https://doi.org/10.1038/nrrheum.2016.23