Lupus Brain Damage Pathway Illuminated

Scientists studying systemic lupus erythematosus (SLE), a chronic, inflammatory, autoimmune disease whose symptoms can include neurological damage, have discovered a possible molecular mechanism for brain dysfunction in some people with the disease.

With support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health, Betty Diamond, M.D., of Albert Einstein College of Medicine, and her colleagues have found that antibodies that attack the DNA of people with lupus can also attack molecules that bind glutamate, a neurotransmitter involved in nerve cell activity. These antibodies, they discovered, can cause neuron death, and are present in the fluid of the brain and spinal cord (cerebrospinal fluid), possibly affecting brain function.

"For people with lupus and their families, potential cognitive and neuropsychiatric symptoms can be particularly distressing," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "This work will help us move ahead in our understanding of the disease's nervous system complications."

In lupus, antibodies that attack double-stranded DNA are known to contribute to kidney problems. The scientists showed that these antibodies also react with similarly structured molecules called NMDA receptors, channels that control the activity of glutamate, the neurotransmitter that stimulates nerve cells. These same antibodies, moreover, are involved in the programmed death of neurons, and the investigators demonstrated their presence in the cerebrospinal fluid of a lupus patient. These factors, they concluded, showed a possible pathway to the neurological symptoms some people with lupus experience.

"Previous studies have documented cognitive dysfunction in patients with SLE, but there has been no explanation for this symptom," said Dr. Diamond. "The excitement of identifying this potential mechanism for cognitive decline is that it suggests therapeutic possibilities."

Lupus is a rheumatic disease with a variety of symptoms and an unpredictable, individualized course. It may affect multiple organs, with common symptoms that include extreme fatigue, painful or swollen joints, unexplained fever and skin rashes. In some patients, lupus can cause headaches, dizziness, memory disturbances, vision problems, stroke, or changes in behavior.

Lupus usually occurs in young women of childbearing years, but many men and children also develop it. African Americans and Hispanics have a higher frequency of the disease than do Caucasians. Both genetic and environmental factors appear to play a role in lupus.

The study was also supported by the Systemic Lupus Erythematosus (SLE) Foundation and the American Heart Association.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the federal 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 our information clearinghouse at 1-877-22-NIAMS or visit the NIAMS Web site at www.niams.nih.gov.

To contact Dr. Diamond, call Ray Fleming at 301-496-8190. To contact the Albert Einstein College of Medicine, call Karen Gardner at 718-430-3101. Reference: DeGiorgio L, Konstantinov K, Lee S, Hardin J, Volpe B, Diamond B. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nature Medicine 2001;7(11):1-5.