By LAWRENCE K. ALTMAN
Published: October 16, 2003
Tests of stored blood of healthy military personnel show that certain antibodies for lupus were formed years before the disease was diagnosed, according to a new study being published today.
The study's authors said the findings provided a more detailed picture of the natural progression of lupus and might lead to discovery of the cause of lupus and safe therapies to prevent the onset of symptoms.
Lupus — its formal name is systemic lupus erythematosus — affects up to an estimated 1.4 million Americans, predominantly women, and is potentially fatal. Lupus usually affects the skin, joints, blood and kidneys, but can harm any part of the body. There are treatments for the disease, but no cure.
Lupus also is one of the so-called auto-immune diseases in which the body produces proteins that attack its own organs instead of foreign infectious agents and tissues. The proteins are known as auto-antibodies, and there are many of them.
Doctors have long linked one known as the antinuclear auto-antibody with a number of diseases, including lupus. But while many people who have the antinuclear auto-antibody later develop lupus, many more do not. There has been no reliable way to predict which people with the antinuclear antibody will develop lupus, in part because scientists have not conducted extensive studies to explore the development of such antibodies in the disease.
As part of a larger project that Dr. John B. Harley began years ago at the Oklahoma Medical Research Foundation to pinpoint the first step that goes awry in the pathway that leads to lupus, Dr. Harley's team broke down various proteins taken from humans into smaller units to help identify the antibodies.
With colleagues from the University of Oklahoma Health Sciences Center, Walter Reed Army Medical Center and the National Institutes of Health, Dr. Harley's team searched the military's medical records for lupus patients.
Dr. Harley said he spent years negotiating with officials of the Department of Defense to use its sera-repository in Washington. The repository contains about 30 million blood samples from more than 5 million military personnel; the samples are kept frozen for research purposes.
The team then tested the blood of 130 service personnel, without knowing their identities, that was initially collected before they developed lupus. They also tested another 130 service personnel of similar age and characteristics who did not develop lupus.
Of the 130 who had lupus, 115, or 88 percent, had at least one autoantibody for lupus up to 9.4 years before the diagnosis, compared with 3.8 percent of the control group, the researchers reported in the New England Journal of Medicine.
"For the first time, this study shows that auto-antibodies occur years before the clinical features of lupus and that specific auto-antibodies are found very close to disease onset," said Dr. Harley, who is also chief of rheumatology at Oklahoma University Health Sciences Center and staff physician with the Veterans Affairs Medical Center in Oklahoma City.
Some auto-antibodies develop years before lupus, others just before the onset of the disease. The auto-antibodies that seemed to correlate with the onset of lupus are known as the anti-nuclear ribonucleoprotein and anti-Sm antibodies.
"It builds a case for the notion that auto-immune disease really starts long before the clinical symptoms arise," said Dr. J. Donald Capra, president of the Oklahoma Medical Research Foundation.
Dr. Harley expressed hope that the new findings would lead other teams to conduct studies to identify patients who might benefit from prophylactic therapy to keep them from developing some of the most serious manifestations of the disease.
Dr. Harley said his team was seeking potential environmental causes like a virus for the abnormal immune response.
Scientists have long theorized that lupus somehow results from an interaction between a virus and a genetic susceptibility to lupus. The new findings renew focus on the Epstein-Barr virus.
"We think the Epstein-Barr virus is the main environmental trigger," Dr. Harley said in a telephone interview.
Dr. Harley said his team believed that Epstein-Barr virus infection was necessary to start the lupus process but required other factors because while the overwhelming majority of Americans are infected with that virus, only a small percentage get lupus.
Epstein-Barr virus causes infectious mononucleosis and has been linked to other diseases.
If scientists proved that Epstein- Barr virus is the specific trigger for lupus, they could then develop new strategies to stop it, Dr. Harley said.
Source: The New York Times