Oct. 15, 2003 -- Long before lupus is diagnosed, things are going awry in the body. New research offers first hints of this progression. It may open a window for early testing and treatment.
The study appears in this week's New England Journal of Medicine.
Lupus, or systemic lupus erythematosus (SLE), is an autoimmune disease, meaning the immune system attacks healthy cells -- in the case of this disease, the whole body is under attack. This causes the typical lupus symptoms of inflammation and damage to joints and the skin, as well as kidneys, bones, the heart, lungs, blood vessels, and the brain.
Lupus affects everyone somewhat differently, and symptoms tend to come and go. Because of this, it can take months or even years for a doctor to make a confident diagnosis.
"For a decade, we have been attempting to pinpoint the first thing that goes awry in the body of a lupus patient," says senior researcher John Harley, MD, PhD, head of arthritis and immunology research at the Oklahoma Medical Research Foundation, in a news release.
Harley's study is the first to show that the production of autoantibodies - an abnormal response in which the immune system makes proteins that attack healthy cells -- occurs years before the visible lupus symptoms become apparent.
Closing In on Lupus
In the study, researchers used blood samples taken from U.S. Armed Forces personnel, available through the Department of Defense. From the military's medical records, they were able to identify 130 servicemen and women who were initially healthy but later developed lupus symptoms.
Blood samples collected from lupus patients before their diagnosis were analyzed and compared with samples from other service personnel without the disease.
"We found that their natural defense system just continued to produce more and more autoantibodies up until the time they were diagnosed with [lupus symptoms]," says co-author Judith James, MD, PhD, with the Oklahoma Medical Research Foundation and the Oklahoma Health Sciences Center, in a news release.
"Unaffected military personnel might occasionally make an abnormal immune response, but those normally resolved spontaneously, and no additional antibodies develop," she says.
Of the 130 patients who developed lupus, 115 (88%) had tested positive for at least one lupus autoantibody up to 9.4 years before the diagnosis, compared with 3.8% of the people not diagnosed with the disease.
"Our results show that new autoantibodies steadily accumulate before the diagnosis and cease to accumulate thereafter" -- possibly due to medications, writes lead researcher Melissa R. Arbuckle, MD, PhD, with the Oklahoma Medical Research Foundation and the U.S. Army Center for Health Promotion and Preventive Medicine in Washington, D.C.
Progression of a Disease
The findings suggest at least three phases of development of lupus:
- The first, asymptomatic phase
- The second phase of benign autoimmunity, when precursor autoantibodies are present but no symptoms show
- The third phase, when more ominous autoantibodies are present, leading to symptoms of lupus and diagnosis
This concept of a "crescendo of autoimmunity culminating in clinical illness" is supported by other studies, Arbuckle writes. Sjogren's syndrome, another autoimmune disorder, also has an early appearance of autoantibodies, which underscores the importance of these antibodies in the disease's development.
In the long term, Harley hopes this study will lead to new and safer treatments for early lupus symptoms. "We are looking at potential environmental causes for this abnormal immune response," he says. "If we are able to identify a pathogen that triggers this process, we could set to work on developing new strategies to stop that pathogen. Some think that a vaccine might be a successful approach."