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Researchers discover 'vitiligo gene', paving the way for new treatments

In a study appearing in the March 22 edition of The New England Journal of Medicine, researchers at St George’s, University of London, the University of Colorado at Denver and Health Sciences Center (UCDHSC) and the Barbara Davis Center for Childhood Diabetes have discovered a connection between a gene and the chronic skin condition vitiligo, as well as a possible link to an array of other autoimmune diseases.

Supported by grants from the National Institutes of Health and funding from the Vitiligo Society (UK) and the National Vitiligo Foundation (USA), the study analysed two independent groups of families enrolled between 1996 and 2005. Samples were obtained from a total of 656 Caucasian individuals from 114 extended families with vitiligo and other epidemiologically associated autoimmune and autoinflammatory diseases from the United States and the United Kingdom.

The researchers began with a study of vitiligo, a distressing condition causing loss of pigment resulting in irregular pale patches of skin, which is visibly detectable in the 0.5% to 1% of people affected by it. The researchers found that persons with vitiligo also have a risk of developing other autoimmune diseases, as do their close relatives, even those without vitiligo. By searching the genome, the researchers discovered that NALP1 – a gene that controls part of the immune system that serves to alert the body to viral and bacterial attacks – was a key gene involved in predisposing to vitiligo and all the other autoimmune diseases that ran in these families.

“The findings give us a clue to why the immune system attacks one of the body’s own tissues: if the sensor NALP1 is over-reactive, it could trigger a response to the wrong stimulus,” said Professor Dorothy Bennett, Professor of Cell Biology at St George’s, University of London, and investigator for the UK arm of this study. “We hope to study exactly how this works, and to learn even more from the other genes that we are working to identify.

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“We are enormously grateful to the patients for their enthusiastic participation, and it’s a great pleasure to find that the first major gene identified is one that suggests new approaches to treatment.”

St George’s, University of London, recruited around half the families who took part in this research, working with the Vitiligo Society. Clinical Co-ordinator Anita Amadi-Myers, of St George’s, worked with patients to get family information and samples. These were sent for analysis to the University of Colorado.

“What’s really exciting for us is that NALP1 hasn’t been specifically implicated in autoimmune diseases before,” said Richard Spritz, MD, director of the Human Medical Genetics Program at UCDHSC and lead investigator for this study. “Since NALP1 appears to be part of our body’s early-warning system for viral or bacterial attack, this gives us ideas about how to try to discover the environmental triggers of these diseases. This finding may also open up new approaches to treatment, possibly for many different autoimmune diseases.”

As a group of approximately 80 disorders that can involve almost any tissue, organ or system, autoimmune and autoinflammatory diseases affect 15 million to 25 million people in the United States. In women, they rank among the top ten causes of death.

Dr. Spritz and his team hope to soon begin organising a clinical trial of a new treatment for vitiligo, based on their NALP1 discovery. Spritz foresees research labs using the information from the UCDHSC study to replicate or test the results in patients with other autoimmune diseases to see how broad potential applications might be. His hope is that the gene NALP1 is also found to be involved in autoimmune and autoinflammatory diseases such as Type 1 diabetes, Addison’s disease, thyroid disease and lupus, among others.

“All diseases are complex, the result of different genes and environmental risk factors acting together in concert. But if NALP1 turns out to be one of the major genes involved in numerous autoimmune diseases, and if we can interrupt its negative effects, we may have the chance to treat many different chronic autoimmune disorders like vitiligo, lupus and psoriasis and perhaps eventually eliminate them altogether,” said Dr. Spritz.

Tamsin Starr | alfa
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