Multiple Sclerosis Autoimmune Response Lacks Memory
A key characteristic observed in the autoimmune response that causes nerve tissue damage in multiple sclerosis patients gives medical researchers entirely novel approaches for combating that disease.
Lerner Research Institute Immunologist Vincent Tuohy, Ph.D., revealed in an article published in the April issue of the Journal of Experimental Medicine that, unlike characteristic immune responses, the autoimmune reaction that attacks and destroys myelin on nerve cells lacks the ability to 'remember' initial molecular structures that serve as immune system targets for Tcells.
"Our immune system normally prepares specific types of white blood cells, the T cells, to recognize and destroy pathogens or infectious agents," Dr. Tuohy explained. "Those cells actually build that allows them to wage a massive defense to combat an infection.
"In an autoimmune response, such as the multiple sclerosis response that destroys brain tissue, T Cells behave differently than normal. They do not remember early response recognition sites, but rather move on to recognize a series of new structures."
Dr. Tuohy's observations of T Cell memory loss was first mice develop a disease similar to that seen in MS patients. Over time, the mice were seen to mount an autoimmune response to an initial immune target. Subsequently, the immune response to the original epitope was not detectable. T cells had become reactive to other sites.
Dr. Tuohy determined that his observations in the mouse were true in humans as well. Following the autoimmune response progress in MS patients over three years, Dr. Tuohy confirmed that initial myelin target sites were 'forgotten' by T Cells in MS patients. The destructive immune cells had moved on to other myelin target sites. He compared this to a fire starting in the kitchen. "It is going to spread from the kitchen to the next room, and the next room after that. By the time the fire trucks arrive, you would normally expect the whole house to be burning
"But not in this case. In the autoimmune response, by the time the fire gets to the next room, it has gone out in the kitchen. It is not what you'd expect."
And, he noted, that divergence from the normal immune response provides a brand new approach for developing therapeutic strategies.
"The Challenge now is to find out why the initial fire goes out and use this knowledge to make the fire go out even earlier before it spreads to the rest of the house."
"As researchers and clinicians, we didn't realize the autoimmune response functioned in this way," Dr Tuohy said. "This gives us a fresh perspective on what has been a baffling problem for both patients and physicians."
About 350,000 Americans have been diagnosed with multiple sclerosis. It can strike at almost any age but is most common among people in their 20s and 30s. It is the leading cause of nontraumatic neurological disability among young adults in North American. Women are almost twice as likely to be diagnosed with MS than men.
Dr. Tuohy's research is representative if the Lerner Research Institute's collaborative approach to molecular medical research. Dr. Tuohy's work is conducted within the Department of Immunology, but complements other work within the Cleveland Clinic Foundation. The Cleveland Clinic, through the Departments of Neurosciences and Immunology, along with and the Mellen Center for Multiple Sclerosis, maintains one of the country's largest programs for the MS treatment and research.
The unique characteristics of the autoimmune response described in Dr. Tuohy's findings may extend beyond the scope of multiple sclerosis to other autoimmune diseases as well. Rheumatoid arthritis and insulin dependent diabetes mellitus are also organ specific autoimmune responses that could be viewed in the new perspective of Dr. Tuohy's medical research contributions.
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Contact: Rob Whitehouse, 216/444-8927 [email protected]
Russ Vanderboom, 216/45830
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