SCIENTISTS TRACK MOLECULAR ėTERRORISTS' IN LUPUS

November 27, 1995
Media Contact: John Cramer
Phone: (410) 955-1534
E-mail: jcramer@welchlink.welch.jhu.edu

Like detectives tracking a terrorist, Johns Hopkins scientists have identified the cause of lupus flareups by figuring out its method of destruction.

Discovering this strategic factor in apoptosis, or cells' built-in "suicide" program, suggests that a treatment could be created around stopping this step in the process, the scientists say. The insight may also shed light on other disorders that involve programmed cell death, such as arthritis, heart disease and neurological diseases.

Comparing the process to strategically placing a few explosives to implode a building instead of scattering them randomly, the scientists say the culprit is an enzyme necessary for normal cell death. But in lupus, the enzyme sets up too many cells for destruction -- a kind of fanatical demolitions expert targeting buildings that should be left alone.

"Now we believe it's not death by a 1,000 cuts, but death by a very few cuts at important places," says Antony Rosen, M.D., the study's senior author and an assistant professor of medicine. "This is the first molecular view of how lupus comes about in the first place. It's also a window on the possible mechanism central to all kinds of disorders involving cell death."

The findings are published in the December issue of the Journal of Experimental Medicine.

"Our next step is determining how to block the enzyme responsible for the cell death involved in lupus flareups, which can be triggered by sunlight and viral infections," says Rosen.

Destruction of the body's own tissue, called an autoimmune response, causes the joint pain, inflammation, skin rashes and other symptoms that mark systemic lupus erythematosus. It primarily affects women of childbearing age, particularly in certain ethnic groups such as African-Americans. In high-risk groups, it affects up to one in 250 women.

The Hopkins team found that many molecules targeted for attack by a lupus patient's immune system are split by the suspected enzyme. The newly created molecule fragments, called "blebs," cluster at the surface of the dying cell where they are attacked by the immune system, which mistakes them for foreign invaders. The research team identified three of the molecules that are split. They are all involved in key pathways required for a cell to survive. "Destroying these molecules seems to be the mechanism of this type of cell death," Rosen says.

Other study authors were Livia A. Casciola-Rosen, Ph.D., and Grant J. Anhalt, M.D. The study was supported by the National Institutes of Health, the Scleroderma Research Foundation and the Dermatology Foundation.


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