Scientists Learn How Lupus Destroys Nervous SystemOctober 31, 2001 By Merritt McKinney
NEW YORK (Reuters Health) - Scientists announced on Wednesday that they may have identified how the autoimmune disease lupus destroys the central nervous system. Antibodies produced by the disease seem to kill nerves by latching on to a receptor on neurons, according to a report in the November issue of the journal Nature Medicine.
The discovery eventually may lead to new therapies for the disease, one of the investigators told Reuters Health. In people with lupus, or systemic lupus erythematosus (SLE) as it is officially known, the immune system loses the ability to differentiate between its own cells and outside invaders, and antibodies attack healthy cells. The condition can vary widely in severity, manifesting as skin rash and arthritis or leading to damage to the kidneys, heart, lungs and brain to varying degrees. There is no cure. The disease disproportionately affects women, particularly those of child-bearing age and of African or Asian descent.
If the central nervous system is affected, the resulting damage can cause a variety of problems including headache, paranoia, mania, schizophrenia and stroke. Exactly how lupus antibodies kill nerve cells has been a mystery, however.
Now Dr. Betty Diamond, of Albert Einstein College of Medicine in New York, and colleagues have discovered in experiments with human tissue and mice that lupus antibodies latch on to a common receptor found on nerves. Once the antibodies attach to these receptors--known as the NR2 subunits of the NMDA receptor--they trigger the death of neurons. The research eventually may lead to new therapies for lupus, one of the study's co-authors told Reuters Health. "New insights into disease mechanism often lead to new therapeutics," said Dr. Bruce T. Volpe, of the Burke Medical Research Institute of Weill Medical College of Cornell University in White Plains, New York.
"Our work suggests a new hypothesis for the clinical symptom of cognitive decline in patients with lupus," he said. "Now we need to test it."
He explained that the antibodies "cross react" with ordinary molecules in the body, meaning that they recognize the molecules by mistake. This "accidental recognition" may destroy the cell, Volpe said. Now that researchers have formulated a new hypothesis about how lupus damages the nervous system, there are many questions to answer, according to Volpe. The next steps, he said, include seeing how frequently the nerve-killing antibodies are present in people with lupus and whether the presence of the antibodies is linked to neurological symptoms.
It will also be important to find out whether the process of cross-reactivity, or accidental recognition, is involved in other immune diseases that affect the nervous system, Volpe said.
The authors of an accompanying editorial agree that the research may open the door to new treatments if it is confirmed. And future research may show that similar types of "cross-reactivities" also play a role in other types of lupus-related tissue damage, according to Drs. Brian L. Kotzin and Elizabeth Kozora, of the University of Colorado Health Sciences Center in Denver.
But the editorialists caution that the results of the experiments, which included samples from only a few lupus patients, are preliminary.
SOURCE: Nature Medicine 2001;7:1175-1176,1189-1193.