|Scientists Implicate Gene in Vitiligo and Other
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
“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.
Additional support for this research was provided by the National
Institute of Allergy and Infectious Diseases, the National Institute
of Diabetes and Digestive and Kidney Diseases, the U.K. Vitiligo
Society and the National Vitiligo Foundation.
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, 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.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.