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Last Updated: Oct 11, 2012 - 10:22:56 PM
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Scientists implicate gene in vitiligo and other autoimmune diseases

Apr 10, 2007 - 4:00:00 AM
The most immediate application of this research might be for the disease that began the research: vitiligo. Doctors usually treat vitiligo with ultraviolet (UV) light to stimulate skin repigmentation. Scientists also know that there is one medication available (approved for treating rheumatoid arthritis) that blocks an inflammatory pathway thought to be controlled by NALP1. The possibility of combining a drug with UV light to improve vitiligo treatment is intriguing, and Dr. Spritz is now interested in finding out more about how the medication might affect people with vitiligo.

 
[RxPG] In a study appearing in the March 22 New England Journal of Medicine, scientists supported by the National Institutes of Health’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered a connection between a specific gene and the inflammatory skin condition vitiligo, as well as a possible host of autoimmune diseases.

Vitiligo is a chronic condition in which melanocytes (the cells that make pigment) in the skin are destroyed. As a result, white patches appear on the skin in different parts of the body. Similar patches also appear on both the mucous membranes (tissues that line the inside of the mouth and nose), and perhaps in the retina (inner layer of the eyeball). The hair that grows on areas affected by vitiligo sometimes turns white.

The researchers began a search for genes involved in vitiligo almost a decade ago with the help of the Vitiligo Society in the United Kingdom. In the beginning we were looking for multiple family members with vitiligo, says Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado at Denver and Health Sciences Center and lead investigator for the study. The researchers sent a questionnaire to members of the society, asking them about their own vitiligo and whether other family members were affected. As part of the questionnaire, they also asked about other autoimmune diseases. What they learned was that vitiligo was very highly associated with a number of other autoimmune diseases, mostly thyroid disease, but also pernicious anemia, rheumatoid arthritis, psoriasis, lupus, Addison’s disease, and adult-onset autoimmune diabetes.

That finding prompted the researchers to study families with multiple affected members and to look for similarities in genes among those who were affected. By searching the genome, they discovered a gene, NALP1, that was key to predisposing people to vitiligo and other autoimmune diseases, particularly autoimmune thyroid disease, says Dr. Spritz. We know that about 20 percent of people with vitiligo also get autoimmune thyroid disease, and this gene may be involved in mediating both of those, he says.

Dr. Spritz says the implications of this finding are exciting. The identified gene controls part of what is called the innate immune system, which is our body’s first defense against infection, he says. When we are attacked by viruses or bacteria, the innate immune system stimulates the inflammatory pathways and calls the rest of the immune system to action. NALP1 is probably a receptor for bacterial or viral signals. We don’t know what these signals are, but now that we know what the gene is, we can use that knowledge to search for the signals that trigger autoimmune disease.

All autoimmune diseases involve the interaction of multiple genes and environmental triggers, he continues. You are born with your genes, but you are not born with these diseases. Something happens. We don’t know what the triggers are that start these diseases, but if we did, maybe we could avoid them or even block the process. In fact, it may even be possible to actually stop the autoimmune disease, he says.

The most immediate application of this research might be for the disease that began the research: vitiligo. Doctors usually treat vitiligo with ultraviolet (UV) light to stimulate skin repigmentation. Scientists also know that there is one medication available (approved for treating rheumatoid arthritis) that blocks an inflammatory pathway thought to be controlled by NALP1. The possibility of combining a drug with UV light to improve vitiligo treatment is intriguing, and Dr. Spritz is now interested in finding out more about how the medication might affect people with vitiligo.

NIAMS Director Stephen I. Katz, M.D., Ph.D., calls the discovery of the NALP1-autoimmunity connection an important advance in the understanding of autoimmune diseases that collectively affect an estimated 15 million to 25 million Americans. The more we understand about these diseases, including the genes that predispose to them and the environmental factors that trigger them, the closer we come to better treatments and even preventive measures, he says.




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