TY - JOUR
T1 - DNA-damaging autoantibodies and cancer
T2 - The lupus butterfly theory
AU - Noble, Philip W.
AU - Bernatsky, Sasha
AU - Clarke, Ann E.
AU - Isenberg, David A.
AU - Ramsey-Goldman, Rosalind
AU - Hansen, James E.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrrheum.2016.23
DO - 10.1038/nrrheum.2016.23
M3 - Review article
C2 - 27009542
AN - SCOPUS:84961392399
VL - 12
SP - 429
EP - 434
JO - Nature reviews. Rheumatology
JF - Nature reviews. Rheumatology
SN - 1759-4790
IS - 7
ER -