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Chaos, hope, and the lupus butterfly theory

April 05, 2016

Yale researchers believe some antibodies associated with lupus may be sources of both chaos and hope in cancer. Borrowing from the Greek legend of Pandora’s box and chaos theory by calling it the “lupus butterfly theory,” the idea was described recently in the journal Nature Reviews Rheumatology.

Lupus, symbolized by the purple butterfly, is a chronic autoimmune disease in which the immune system attacks healthy tissues. The disease, often characterized by a butterfly-shaped rash, carries an unusual cancer risk profile, with a small increase in overall risk but reduced rates of certain malignancies, such as breast cancer. The reasons for this risk profile are unknown, but the lupus butterfly theory now proposes that lupus antibodies are a contributing factor.

Antibodies that bind to DNA, the genetic blueprints for life, are a hallmark of lupus. Research led by James E. Hansen, M.D, assistant professor of therapeutic radiology, has shown that some of these antibodies actually damage the DNA inside living cells, and that some cancer cells are much more sensitive to them than normal cells. Based on these findings, Hansen and colleagues theorize that certain cancers are suppressed in lupus patients due to a protective effect mediated by the DNA-damaging antibodies.

Consistent with this idea, cancers that are underrepresented in lupus are associated with genetic defects that make them vulnerable to DNA damage. So, even though lupus antibodies that attack DNA may contribute to immunologic chaos, they may also be considered sources of hope by providing protection against certain malignancies. Furthermore, there is hope that these antibodies may be able to be harnessed for use as new therapies against tumors that are highly vulnerable to DNA damage.

“It’s exciting that our efforts to apply lupus antibodies to cancer therapy may also help to answer unresolved questions about the associations between autoimmunity and cancer,” said Philip W. Noble, PhD, first author on the paper and postdoctoral research associate in the Hansen lab.

Hansen added, “Chaos theory suggests that a regular butterfly can change the weather just by flapping its wings. I’m hoping that when a lupus butterfly ‘flaps its wings’ it can change the face of cancer therapy.”

Co-authors include Dr. Sasha Bernatsky, Dr. Ann E. Clarke, Dr. David A. Isenberg, and Dr. Rosalind Ramsey-Goldman.

Submitted by Emily Montemerlo on April 05, 2016