December 17, 2007

IBM T-cell Profiles Suggest Autoimmunity Role

Support for the idea that autoimmunity (self-immunity), a mistaken attack by the immune system on the body’s own tissues, is part of the disease process in nonfamilial inclusion-body myositis (IBM) was recently demonstrated in studies from the laboratory of Marinos Dalakas at the National Institutes of Health in Bethesda, Md.

Some experts have argued that IBM is primarily an inflammatory, autoimmune disease, while others have argued that it’s primarily degenerative in nature. There is evidence for both processes, though which is primary remains debatable.

Dalakas and colleagues, who published their results in the Oct. 23 issue of Neurology, studied muscle and blood cells from 12 people with nonfamilial (sporadic) IBM and compared the two kinds of cells with each other and with blood cells from unaffected people.

They found that certain proteins on the surfaces of the immune system’s T-cells were different in muscle compared to blood in people with IBM, with the muscle T-cells showing a narrower range of specific surface proteins than the blood cells. Both kinds of cells showed less variation in their surface-protein patterns than did blood T-cells from people without the disease.

The surface proteins the researchers analyzed are those that make up the T-cell receptors, the parts of the cells that participate directly in an immune response.

The results, the investigators say, suggest that the T-cells in IBM are specifically reacting against the patients’ muscle fibers, and that after they enter the fibers from the bloodstream, they begin to specialize in this anti-muscle reaction.

The T-cells that are still in the bloodstream don’t have the same degree of anti-muscle specification, even in the IBM patients, and the T-cells from the unaffected samples don’t show any such specification.

When the researchers compared T-cells in muscle biopsy samples taken from people with IBM a year after the initial samples were examined, they found the degree of specificity of the surface proteins was essentially unchanged.

They say their findings support the view that muscle-fiber proteins are a stimulus for an undesired, chronic response by the immune system in this disease.

They say further probing of the response should help clarify the relationship between inflammation and degeneration in IBM and offer means of “better customizing therapeutic strategies.”