"For a decade, we have been attempting to pinpoint the first thing that goes awry in the body of a lupus patient," said John Harley, M.D., Ph.D., head of the arthritis and immunology research program at OMRF and senior author of the study. Harley also serves as chief of rheumatology at OUHSC and staff physician with the Veterans Affairs Medical Center in Oklahoma City.
"For the first time, this study shows that autoantibodies occur years before the clinical features of lupus and that specific autoantibodies are found very close to disease onset," Harley said.
In lupus and other autoimmune diseases, the immune system loses its ability to differentiate between foreign substances and its own cells and tissues, causing the body to attack itself. Lupus can affect any part of the body--most commonly the skin, joints, blood and kidneys--and can be life-threatening. The disease primarily strikes women and has no known cure.
In conducting this new study, the researchers used the Department of Defense Serum Repository in Washington, D.C., which contains approximately 30 million blood samples collected from more than five million U.S. Armed Forces personnel. From the military's medical records, the scientists were able to identify 130 servicemen and women who were initially healthy but later developed lupus. The scientists then analyzed blood samples collected from the lupus patients prior to their diagnosis and compared them with samples from matched service personnel without the disease.
"In patients with lupus, we found that their natural defense system just continued to produce more and more abnormal responses--autoantibodies--up until the time they were diagnosed with the disease," said Judith James, M.D., Ph.D., of OMRF and OUHSC, one of the study's co-authors. "Unaffected military personnel might occasionally make an abnormal immune response, but those normally resolve spontaneously, and no additional antibodies develop."
The study, noted Harley, holds important clinical value. "We hope that the new findings will lead to studies that will help identify those who would benefit from prophylactic therapy," he said. "This would give us a chance to intervene and keep those people from developing some of the most serious manifestations of the disease."
In the long term, Harley hopes this study will lead to new and safer therapies. "We are now looking at potential environmental causes for this abnormal immune response," he said. "If we are able to identify a pathogen that triggers this process, then we could set to work on developing new strategies to stop that pathogen. Some think that a vaccine might be a successful approach."
The other authors of the study are Melissa Arbuckle, M.D., Ph.D. (OMRF, Walter Reed Army Medical Center), Micah McClain, Ph.D. (OMRF, OUHSC), Mark Rubertone, M.D. (U.S. Army Center for Health Promotion and Preventive Medicine), R. Hal Scofield, M.D. (OMRF, OUHSC, VAMC Oklahoma City) and Gregory Dennis, M.D. (Walter Reed, National Institute of Arthritis and Musculoskeletal Skin Diseases). The study was funded by the National Institute of Arthritis and Musculoskeletal Skin Diseases and the National Institute of Allergy and Infectious Diseases.
About OMRF:
OMRF (www.omrf.org) is a nonprofit biomedical research institute dedicated to understanding and curing human disease. Its scientists focus on such critical research areas as Alzheimer's disease, cancer and cardiovascular disease. OMRF is home to Oklahoma's only Howard Hughes Medical Institute investigator and only member of the National Academy of Sciences in the area of biomedical research.
Journal
New England Journal of Medicine