Autoantibodies Precede Disease in Lupus Patients

A new study funded largely by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reveals that people diagnosed with systemic lupus erythematosus (lupus) �� an autoimmune disease in which the body attacks its own tissues �� have autoantibodies in their blood years before the symptoms of lupus appear. The early detection of autoantibodies �� proteins that attach to the body's healthy tissues by mistake �� may help in recognizing those who will develop the disease and allow physicians to monitor them before they might otherwise be noticed.

Senior author John Harley, M.D., Ph.D., of the Oklahoma Medical Research Foundation and the University of Oklahoma, and his colleagues there and in other institutions, tested blood from 130 U.S. armed forces servicemen and women, without knowing their identities, who were once healthy but later developed lupus. Using many years of previously collected samples from the Department of Defense Serum Repository, the researchers compared samples from the lupus patients to samples from those who never developed lupus. When testing early samples from both groups, they found that those with lupus had the autoantibodies in their blood for months to years before symptoms appeared. Some of the autoantibodies, such as antinuclear antibody, had been present longer than others. The lupus autoantibodies, say the authors, tend to accumulate in the blood in a predictable pattern up until diagnosis, when the rate of new autoantibodies slows.

"We don't know whether the virtual halt in the accumulation of new autoantibodies is a result of therapy now typically used or whether the relative stability in the autoantibodies found after diagnosis is a feature of the natural history of lupus," said Dr. Harley. "Certainly, this observation reminds us of how important diagnosis is for what subsequently happens in the immune system of the patient."

NIAMS Director Stephen I. Katz, M.D., Ph.D., said "Identifying such patterns in disease progression may lead researchers to understand what causes autoantibodies to appear when they do and how they contribute to the disease." NIAMS researcher Gregory Dennis, M.D., a coauthor of the study, said, "Lupus and other autoimmune diseases often go untreated for years and are diagnosed only after damage to the body tissues has occurred. Findings such as these, which will help us identify and monitor people who may develop these diseases, are extremely valuable."

Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels and brain. People who have lupus may have many different symptoms, but some of the most common ones include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes and kidney problems. Many more women than men have lupus. It is three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian and Native American descent.

Other institutions taking part in the study included NIAMS, the Department of Veterans Affairs, Walter Reed Army Medical Center and the U.S. Army Center for Health Promotion and Preventive Medicine. Funding was also provided by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources, both part of the Department of Health and Human Services' National Institutes of Health.

To contact Dr. Harley, call Adam Cohen at the Oklahoma Medical Research Foundation at (405) 271-7159.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

Arbuckle M, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. NEJM 2003;349(16):1526-33.