Gene Implicated in Vitiligo and Other Autoimmune Diseases

Scientists 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 scientists 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, said Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado at Denver and Health Sciences Center (Denver, CO, USA) and lead investigator for the study.

Members of the society received a questionnaire 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.

A gene, NALP1, was the key to predisposing people to vitiligo and other autoimmune diseases, particularly autoimmune thyroid disease, according to Dr. Spritz. We know that about 20% of people with vitiligo also get autoimmune thyroid disease, and this gene may be involved in mediating both of those, he said. The identified gene controls part of what is called the innate immune system, which is the body's first defense against infection.

Dr. Spritz reported that the implications of this finding are exciting. 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. 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.”

The U.S. National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; Bethesda, MD, USA) director Stephen I. Katz, M.D., Ph.D., called the discovery of the NALP1-autoimmunity connection an important advance in the understanding of autoimmune diseases that collectively affect an estimated 15–25 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 said.

The study appeared in the March 22, 2007, issue of the New England Journal of Medicine.


Related Links:
University of Colorado at Denver and Health Sciences Center
National Institute of Arthritis and Musculoskeletal and Skin Disease