Department of Medicine researcher mounts new attack on lupus

Dr. Keith B. Elkon, head of the Division of Rheumatology in the Department of Medicine and a veteran lupus investigator, is taking a novel approach to this disease, which affects approximately a half million Americans, mostly young women. He has received a $447,000 award from the Alliance for Lupus Research to develop a way of interrupting the progress of lupus without suppressing the body’s natural defenses. And he is building a team of experts to pursue other assaults on this devastating disorder.

Lupus--also known as systemic lupus erythematosus or SLE--is an autoimmune disease that predominantly affects young women, most commonly those of African-American, Hispanic, Asian, and Native American descent. Lupus often begins with a skin rash and joint pains, although it can affect virtually any organ in the body and is, potentially, a life-threatening disease.

In an autoimmune disorder like lupus, the immune system produces antibodies that attack the body’s own cells and tissues as if they were foreign matter. These "auto-antibodies" bind to proteins and nucleic acids in the blood, forming "immune complexes" which cause inflammation, pain, and damage in various parts of the body.

Traditionally, lupus has been treated with anti-inflammatory drugs, corticosteroids (steroids), and--in severe cases--cytotoxic drugs that suppress the entire immune system. Steroids and cytotoxic drugs can have severe side effects. Newer "biologic" drugs currently in clinical trials may be safer because they target only one protein or pathway in the immune system.

Dr. Elkon, professor of medicine, has had a research interest in lupus for more than 20 years. His new grant will support a project called "Lysis of Immunostimulatory Nucleoproteins in SLE" Its goal is to degrade the nucleic acid component of the immune complexes, rendering them unable to deposit in tissue or activate inflammatory receptors.

"Although the biologic therapies for SLE are more selective compared to current therapy, they still do block natural defense mechanisms in the body" said Dr. Elkon. "Also, none of the existing treatments target the actual immune complexes that induce the inflammatory process. The new project therefore represents a novel approach to therapy and one predicted not to suppress the body’s natural defenses.

The Division of Rheumatology at UW focuses on patient care, clinical trials, and basic research in lupus. Current research in the division includes the study of hormones that are thought to play a role in the female predominance of lupus, the causes of brain lupus, the stimuli responsible for generating autoantibodies, and attempts to break up immune complexes to make them harmless. This research is supported, in part, by the National Institutes of Health, the Lupus Research Institute, the Alliance for Lupus Research, and Leap for Lupus.

Elkon is building a translational research group in his division to pursue more effective therapies for lupus and other autoimmune diseases. He recently recruited Jeffrey Ledbetter, PhD, a founder of the local biotechnology company Trubion and co-inventor of the biologic Abatacept (Orencia), and he plans to recruit to the division another basic immunologist with expertise in human immunology.

Patient information on lupus can be obtained from the Lupus Foundation of America (http://www.lupus.org). Donations to support lupus research in the Division of Rheumatology may be sent to: Division of Rheumatology, c/o Kelli Trosvig, Box 356428, University of Washington, 1959 NE Pacific St., Seattle, WA 98195.