Less toxic therapies on the horizon - Autoimmune Diseases

Autoimmune diseases--which include lupus, rheumatoid arthritis, myasthenia gravis, Grave's disease, and small vessel vasculitis--are caused when antibodies produced by an individual's immune system mistakenly are directed to attack the body's own tissues. University of North Carolina at Chapel Hill researchers, however, have discovered that patients with autoimmune disease harbor antibodies reactive to a normal "self" protein (the autoantigen of this disease), as well as to its mirror image protein. In other words, parallel to the existence of the normal "self" proteins are the proteins complementary to "self" proteins.

Ronald Falk, Thurston Professor of Medicine and chief of the School of Medicine's Division of Nephrology and Hypertension, likens the research team's observations and eventual findings to the work of M.C. Escher, a well-known graphic artist whose drawings incorporate optical illusions and unconventional patterns that may elude the viewer's eye at first glance. "In an Escher drawing, the eye focuses on one image, but there is a parallel image that interconnects with the dominant image. [The University of North Carolina] proposes that in autoimmunity, the parallel image has been overlooked in the past, and may be, in fact, the culprit and trigger for autoimmunity."

That discovery led the researchers to propose that the genesis of autoimmunity is the production of an antibody against a protein complementary to a normal "self" protein. This event initiates a chain reaction leading to the progressive evolution of antibodies that react against "self." The key to understanding this sequence is in clarifying the interactions of proteins with their corresponding counterparts. The novelty here is the discovery of mirror image immunologic components as primary in triggering an autoimmune response.

Why an individual's immune system makes these errors has long been a mystery, and Falk's findings may explain how and why such mistakes occur--and offer a new theory for the development of autoimmunity. However, the source of the complementary, or mirror image, proteins remains unknown. They may be carried by microbes. Some evidence suggests that patients produce the microbes themselves by an irregular transcription. Transcription is the process of constructing a messenger RNA using a DNA molecule as a template with a resulting transfer of genetic information to the messenger RNA.

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