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Markers for Lupus Seen Years Before Diagnosis

Finding is a new step in understanding the autoimmune disease

WEDNESDAY, Oct. 15, 2003 (HealthDayNews) -- Patients with lupus develop antibodies for the disease up to nine years before symptoms occur, researchers report.

Lupus, a disorder of the immune system, shows itself in a variety of ways and produces antibodies that attack the immune system.

"That self-destructive process is why the disease is called an autoimmune disease," says Dr. John Harley, the lead researcher and a professor of medicine at the Oklahoma Sciences Research Center and the University of Oklahoma Health Sciences Center.

Fifty years ago, lupus had a mortality rate of 50 percent. Now the mortality rate is less than 10 percent, Harley says. However, lupus remains a life-threatening and life-altering disease, he adds.

Writing in the Oct. 16 issue of the New England Journal of Medicine, Harley and his colleagues report for the first time that these antibodies are present years before lupus becomes symptomatic.

The specific antibodies are antinuclear, anti-double-strand DNA, anti-Ro, anti-La, anti-Sm, anti-nuclear ribonucleoprotein, and antiphospholipid.

The researchers looked for these antibodies in blood samples from 130 lupus patients. The blood samples were collected years before symptoms of lupus appeared.

"The typical patient who gets lupus has positive antibodies in their blood years before the diagnosis," Harley says. Of the 130 patients, 115 had one or more of these antibodies up to nine years before symptoms appeared, the investigators report.

"One of the surprising findings was that there appears to be an order in which antibodies appear. Anti-nuclear ribonucleoprotein and anti-Sm antibodies appeared just before diagnosis, while other antibodies, like anti-Ro and anti-La, appear years and years before diagnosis," Harley notes.

He adds that anti-double-strand DNA antibodies appear about two years before diagnosis.

Harley believes that his findings indicate that patients who test positive for any of these antibodies are the ones most likely to develop lupus.

However, these results should not be taken as a recommendation to test people for these antibodies, he adds. This is only preliminary data, he says.

What is needed, according to Harley, is a clinical trial that would treat people who have these antibodies with Plaquenil, a drug that inhibits lupus in patients with mild disease, to see if this treatment would prevent the onset of lupus.

The problem, Harley says, is that not all people with these antibodies develop lupus.

"There are people with positive tests who go on for years and years, if not decades and decades, without developing lupus. Right now, you can't tell which patients are at high risk for lupus and which are not, based on the test alone," he adds.

The latest findings move researchers closer to having better therapies for lupus in the future. Right now, though, there is no implication for treating patients with lupus or those who are at risk for lupus, Harley says.

Harley's team continues to look into both genetic and environmental causes of lupus. On the genetic side, they have collected data from 400 families in which at least two members have developed lupus. So far, they have identified 12 genetic effects to the disease, and they are now working to identify the specific genes involved.

The researchers have also been doing immunochemical studies of the interaction of antibodies and antigens. Their findings have shown that Epstein-Barr virus may play a role in the development of lupus.

Dr. Robert Shmerling, an associate professor of medicine at Harvard Medical School and author of an accompanying journal editorial, comments that the findings are "interesting and intriguing."

However, Shmerling is not sure they are useful in treatment right now. "I don't think we should be screening people, and I doubt that if we did, that it would lead to an earlier diagnosis of lupus," he says.

"Even if the antibodies were absolutely perfect in predicting lupus, there is no preventive therapy," he adds.

More information

To learn more about lupus, visit the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the Lupus Foundation of America.

SOURCES: John Harley, M.D., Ph.D., professor of medicine, Oklahoma Sciences Research Center and the University of Oklahoma Health Sciences Center, Oklahoma City; Robert Shmerling, M.D., associate professor of medicine, Harvard Medical School, Boston; Oct. 16, 2003, New England Journal of Medicine
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