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Scientists stop autoimmune disease without shutting off immune system

Skin is our first line of defense against infection. But people with a rare, life-threatening autoimmune disease called pemphigus vulgaris lack that protection because their immune system attacks the proteins that hold skin cells together. They develop severe blisters and raw sores as the top layer of their skin falls apart, leaving them extremely vulnerable to infection.

The development of drugs that completely suppress the immune system offered a lifeline to patients with pemphigus vulgaris (PV) and other autoimmune disorders, but the drugs themselves can be lethal and often cause serious side effects.

Now, researchers at the University of North Carolina at Chapel Hill have found a safer, more effective way to treat PV patients. In mice, the researchers used a known compound to turn off the signals that trigger skin damage without suppressing the immune system. Similar drugs being developed for human use could offer a potential treatment for PV, the researchers said.

The results appear in the Aug. 22 issue of Proceedings of the National Academy of Sciences. The research was funded the National Institutes of Health."Even if we can't block the immune response, if we can understand the mechanisms behind the damage it causes, we can block that damage," said Dr. David S. Rubenstein, associate professor in the departments of dermatology and pathology in the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. "Targeting these specific events in the cell could enable us to more effectively and safely treat patients."

Rubenstein has previously shown an enzyme called p38 is part of the mechanism by which pemphigus vulgaris autoantibodies cause damage. Autoantibodies are immune-system cells that attack the body's own tissues.

In a mouse model of pemphigus vulgaris, the researchers prevented blistering and other signs of the disease by injecting a drug that inhibits the p38 enzyme. Tests showed t
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Source:University of North Carolina School of Medicine


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