Systemic lupus erythematosus, commonly referred to as simply "lupus," is an autoimmune disease that affects more than half a million Americans. In lupus, as well as in other autoimmune diseases, the body's immune system attacks components of the body it is designed to protect; the results may affect several organ systems. In up to 75 percent of people with lupus, there is a wide variety of associated neurological and psychiatric syndromes, including cognitive, behavioral, emotional and motor problems.

While little has been known about how lupus affects the central nervous system (CNS), new research is providing some clues. Findings by scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) are not only helping to explain the mechanism behind nervous system involvement, but may also lead to ways to stop it.

NIAMS-supported researcher Betty Diamond, M.D., of Columbia University in New York, reported that a subset of antibodies to DNA can be found in the blood and the brain of lupus patients with cognitive problems. These anti-DNA antibodies bind to specific receptors (NMDA receptors) on nerve cells in the brain. In the culture dish, binding of these anti-DNA antibodies to nerve cells results in the death of the cells. The next step was to see if the same thing occurred in laboratory animals.

In subsequent studies, Dr. Diamond and her colleagues induced mice to produce these anti-DNA antibodies and have them circulating in their blood. However, the antibodies did not affect the nervous system unless the blood-brain barrier was broken, allowing the antibodies access to the brain. In mice where the blood-brain barrier was broken, antibodies were found bound to the neurons in a specific area of the brain that helps regulate emotion and memory. Tests for cell death in that area of the brain were positive. Behavioral tests on the mice also revealed impaired cognitive function and memory.

Perhaps more important was the finding that the nerve cell binding and its damage could be prevented. Mice with these circulating antibodies were given a drug that inhibits the NMDA receptor. The antibodies bound to the receptors in the brain when the blood-brain barrier opened; however, the drug blocked the nerve cell damage in the brain with no apparent loss of memory.

While the studies thus far have been confined to laboratory animals, researchers say the findings suggest that drugs that inhibit the NMDA receptor may eventually be a useful therapy for people with lupus.

The mission of 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.

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Czeslawa K, et al. Cognition and immunity: antibody impairs memory. Immunity 2004;21:179-188.