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Spotlight on Research 2009
April 2009 (historical)
NIAMS Researchers Discover New Treatment Target for Autoimmune Blistering Skin Diseases
Researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have identified a mechanism in mice that contributes to the development of pemphigus foliaceus (PF), an autoimmune disease that causes skin blistering. The discovery could generate novel therapeutic strategies for the treatment of the disease.
In PF, immune system cells that normally defend against harmful things, like bacteria and viruses, also react to the body's own proteins in the skin. These skin proteins usually act as a glue to help hold the layers of skin cells together in order to form a protective barrier against the outside of the body. However, with PF, autoantibodies—proteins that attach to the body's healthy tissues by mistake—target proteins in skin cells that keep the layers of the skin together, causing the skin cells to lose their ability to stick together which results in blistering. Since the skin is the first line of defense against infectious agents, blistering can lead to serious health problems.
The standard treatment for autoimmune diseases uses therapies that suppress the immune system, thereby reducing its attack on the body. However, with the increased risk of infection in people with PF, the use of immune-suppressing therapies can decrease the body's ability to fight off infections. Researchers have been looking for alternative strategies to block the immune system's attack on skin proteins, without increasing the risk of infection.
David S. Rubenstein, M.D., Ph.D., at the University of North Carolina School of Medicine and his colleagues studied PF in mice and found that protein p38 mitogen-activated protein kinase (p38 MAPK) is modified and activated in the skin cells of mice with the disease. When the researchers pretreated the mice with a p38 MAPK inhibitor before injection with human PF antibodies, they found that the treatment prevented the formation of skin blisters, potentially without reducing the ability of the immune system to fight off infection. The study appeared in the December 2008 issue of The American Journal of Pathology.
These findings provide support to the idea of targeting specific aspects of autoimmune response, instead of using strategies that broadly impact the body's immune system. Researchers are already studying the role of p38 MAPK in people with other diseases, including rheumatoid arthritis and pemphigus vulgaris, a skin disease related to PF.
The study was also supported by the National Institute of Allergy and Infectious Diseases (NIAID).
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.
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Berkowitz P, Chua M, Liu Z, Diaz LA, Rubenstein DS. Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering via p38 mitogen-activated protein kinase-dependent signaling in the skin. American Journal of Pathology. 2008;173(6):1628-1636. Epub 2008 Nov. 6.