Lupus brain damage pathway illuminated

November 19, 2001

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

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.

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.

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.