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Spleen Cells May Prove Effective Target for Lupus Treatment

Researchers discover the organ is origin of the disease in 'transgenic' mice

THURSDAY, Sept. 14, 2006 (HealthDay News) -- Research done on mice specially bred to develop lupus has uncovered an area of the spleen that may give rise to the disease.

The area is called the marginal zone of the spleen and it appears that this is where B cells from the immune system go awry and turn into cells that attack the body's own tissues and organs, researchers say.

"This current work gives rise to new possibilities for targeted therapies that are perhaps much milder and more effective than current therapies," said the study's lead author, Thomas Enzler, a visiting scholar, internist and immunologist at the University of California, San Diego. However, he was quick to add that it would be a long time before any such potential therapy could be available for humans.

Results of the study were published Thursday in the online edition of the journal Immunity.

Lupus is an autoimmune disease in which the immune system mistakenly attacks the body's tissues and organs. The disease can affect the joints, kidneys, lungs, brain, blood or skin. As many as 1.5 million Americans have lupus, and the disease is far more common in women than in men, according to the Lupus Foundation of America (LFA).

Previously, researchers had developed a mouse version of lupus. These mice are bred to overproduce an immune system hormone (cytokine) known as B-cell activating factor (BAFF). In humans with lupus, the BAFF cytokine is often present in much higher-than-normal levels. B cells produce antibodies. Normally, antibodies are produced to protect against viruses and bacteria. In the case of someone with lupus, however, the B cells produce autoreactive antibodies. This means the antibodies attack normal, rather than diseased, tissue.

When the mice overproduce BAFF, they develop lupus, though the mouse version isn't exactly the same as the human version.

The UCSD researchers transplanted some of the cells from the spleens of the marginal zone of the lupus mice into mice that didn't have their own B cells. Lupus-like antibodies began to develop in these mice immediately.

The researchers also removed the spleens of some of the lupus mice when they were in the early stages of developing the disease, or the scientists interrupted the production of the B cells. When they did this, lupus was diminished or prevented.

"It seems to be that the marginal zone is really important for developing autoimmune disease in transgenic mice," Enzler explained.

Dr. Joan Merrill, medical director of the Lupus Foundation of America and head of the clinical pharmacology research program at Oklahoma Medical Research Foundation, said, "This is an exciting scientific paper."

But, Merrill said, people with lupus shouldn't rush to their doctors to remove their spleens. "If a lupus patient has a splenectomy, the disease doesn't go away," she said, explaining that sometimes lupus patients have to have their spleens removed due to complications of the disease, and it doesn't cure lupus.

She also pointed out that this study was done in mice and the human immune system doesn't work in exactly the same way as the mouse immune system does.

Still, Merrill added that with this study and other research, "We're beginning to unravel some of the mysteries surrounding lupus, and I'm cautiously optimistic about the future. We're trying to find better targets and develop better and safer medicines."

More information

To learn more about lupus, visit the Lupus Foundation of America.

SOURCES: Thomas Enzler, Ph.D., visiting scholar, internist and immunologist, University of California, San Diego; Joan T. Merrill, M.D., medical director, Lupus Foundation of America, and head, clinical pharmacology research program, Oklahoma Medical Research Foundation, Oklahoma City; Sept. 14, 2006, Immunity online
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