Scientists uncover part of mystery surrounding lupus

Medical Center researchers have uncovered part of the mystery behind lupus, one of the leading causes of natural death for young women.

Lupus is a crippling and sometimes fatal disease that strikes most often in otherwise healthy women of child-bearing age and can damage kidneys, heart, skin and other organs. The disease affects about one in 2,000 people but is five times more common in women as in men. Patients with lupus make antibodies to parts of their own bodies, causing their immune systems to attack their own tissue rather than infections or tumors.

Led by Dr. Gary Gilkeson, an assistant professor of rheumatology immunology at the Veterans Affairs Hospital, the Duke team has been studying varieties of lupus that attack the body's own DNA and last month published an article showing that bacterial DNA can bring on symptoms in mice genetically prone to the disease. The research suggests that bacterial DNA could provoke the disease in humans as well.

By discovering potential factors in the development of the disease, scientists have shown that lupus is predisposed and does not develop late in life. Such findings may lead to new ways to prevent or lessen symptoms, Gilkeson said.

Earlier research had shown that mammals do not respond to injected mammalian DNA, but that bacterial DNA does provoke an immune response. To investigate the cause of this phenomenon, scientists studied the responses of normal and lupus-prone mice to injections of mammalian and bacterial DNA.

While neither category of mouse showed any reaction to the mammalian DNA, crucial differences appeared in their responses to the bacterial DNA. Normal mice produced antibodies specific to the foreign DNA, while the lupus-prone mice developed antibodies that not only attacked the foreign DNA but also reacted to their own genetic material.

The researchers are in the process of planning a multi-institutional study that will investigate the response of patients already diagnosed with the disease.

"We know that bacterial infections and poor living conditions seem to correlate with more severe lupus symptoms," said Dr. David Pisetsky, study author and co-director of the Duke University Arthritis Center, in a statement. "This study suggests that bacterial infections could be the trigger that initiates or worsens the disease. With this new evidence, we should be recommending that lupus patients take precautions to reduce contact with infectious bacteria."

Other scientists working with lupus are encouraged by the findings, but said they are cautious when looking ahead to further application of the research.

"If we know how lupus is caused then we can know the treatment," said Dr. Ram Singh, research fellow in rheumatology at the University of California at Los Angeles. Singh is part of a research group that looks at the self-proliferation of the DNA-attacking antibodies in lupus patients.

Although many scientists have attempted to study the connection between DNA and lupus antibodies, the Duke group is one of the few to have results, Singh said. While he does not dispute the validity of the Duke research, Singh said he is unsure whether the recent work will have much of a direct impact on human lupus.

"The general feeling [among lupus researchers] is that DNA does not induce antibodies in general," Singh said. "I don't know how relevant [the Duke research] is in the spontaneous human disease."

Nonetheless, Gilkeson said the research will aid scientists in the quest to discover a cure.

"Now that we have a mouse model in which we can induce lupus, we can begin to ask why and how the immune system goes awry," Gilkeson said. "This model will help tremendously in separating the causes of lupus from the effects of the disease."

The scientists reported their findings in the March issue of the Journal of Clinical Investigation.

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