Could lead to safe,effective treatments.
Tuesday, February 2, 1999, in the San Jose Mercury
BY LISA M. KRIEGER
Mercury News Staff Writer
Classifieds & Services Bay Area scientists have identified the cells that trigger one of the immune system's most tragic mistakes, the debilitating neurological disease called multiple sclerosis.
Immune cells called antibodies, which normally protect against outside invaders, confusedly attack and destroy the lining of the nervous system, University of California-San Francisco researchers report in the current issue of the journal Nature.
Although the reason for this internal civil war remains unknown, the discovery could lead to a safe and effective treatment of a disease that is now incurable, according to the UCSF team.
Patients have had to rely on broad-spectrum immunosuppressants to fight symptoms, which range from a this page mild tingling to paralysis. The new discovery could lead to more targeted therapies against MS, which affects approximately 350,000 Americans.
"It is really quite exciting," said Virginia Ladd, executive director of the American Autoimmune and Related Diseases Association in Detroit. "For a long time, we've been looking to prove that multiple sclerosis is an autoimmune disease -- so by finding antibody involvement, it indicates that immunity is at play."
Researchers have suspected that multiple sclerosis is a disease of "autoimmunity," in which the body turns against itself.
But teasing out the related and often intertwined components of the immune system has been daunting.
The UC scientists took a close look at brain tissue obtained from patients during active phases of multiple sclerosis and found antibodies attacking the membranous sheath that insulates the long nerve fibers of the spinal cord and brain.
The inflammation, destruction and disintegration of this insulation, called myelin, impedes the ability of nerve cells to communicate.
When that happens, messages cannot be sent from the brain to the muscles.
"Thirty years ago, we suspected antibodies played a role, but we lacked the technology to show it," said lead author Dr. Cedric Raine, assistant professor of neurology at UCSF.
"The significance here is that for the first time we've been able to localize antibodies to the myelin sheath and to demonstrate their involvement in myelin breakdown."
MS is the second most common neurological cause of disability of young U.S. adults, after head trauma. Rarely diagnosed in children or the elderly, it begins in two-thirds of all patients between the ages of 20 and 40.
The disease can strike at any time, leaving persons blind or paralyzed for days, months or forever. It can just as quickly go into remission, only to return later.
MS symptoms are diverse, reflecting the size and severity of the damage.
Eventually, the active inflammation subsides.
Scientists credit offsetting influences of other immune cells, called "suppressor" cells. Depending upon the severity and duration of inflammation, remyelination and recovery of function may occur.
The immune system can be both a friend and foe. It is a friend when it protects against disease. But it is a foe when it attacks life-saving transplants -- or, as in the case in MS and at least 80 other diseases, including lupus and arthritis -- mistakenly turns on the body's own tissues.
Only two decades ago, immunologists didn't understand immune responses. But with the cloning of genes for several key immune system components in the early 1980s, both normal and abnormal responses have been demystified.
Cause still unknown
The underlying cause of rogue immune reactions remains a mystery. There are several hints that MS might be genetic.
For instance, it is primarily a Caucasian disease, especially affecting
those of northern European ancestry; its
prevalence is low in African blacks and Asians. Like many autoimmune disorders, MS disproportionately affects women. The ratio of women to men is about 2 to 1.
Recent studies suggest that eight or more genes governing control of immune function, located on chromosome 6, may affect the potential to develop MS.
But genetic tendencies are only part of the story. If the disease were completely genetic, 100 percent of identical twins of MS victims would be affected; instead, they are affected in only 30 to 50 percent of cases. Non-twin siblings and fraternal twins are affected in about 5 percent of cases, while the general population has a rate of about 0.1 percent.
Genes contribute susceptibility to MS, but an unknown environmental "trigger," such as a viral infection, may tip the balance toward developing the disease.
Antibodies, produced by the body's B cells, are not the sole culprit, according to the UCSF scientists. Another type of immune system cells -- called T cells -- were once the prime suspects, but are now thought merely to contribute to the destruction of myelin. The principal role of T cells may be their ability to penetrate the blood-brain barrier, creating an opening that ushers in a cascade of antibodies.
This new advance in immunology could lead to better medications to prevent or ameliorate the symptoms of disease, the scientists wrote.
MS is generally treated with powerful doses of immune-suppressing steroid
hormone, but this drug has serious side effects and does not permanently
retard the progression of disability.
©1999 Mercury Center.