In a research study appearing in the 22nd March 2007 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, 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 diseases such as autoimmune thyroid disease, rheumatoid arthritis, psoriases, adult-onset autoimmune diabetes, pernicious anaemia, lupus and Addison disease.

The researchers began with a study of vitiligo and they found that people with vitiligo were also predisposed to other autoimmune diseases, as were their close relatives, even those without vitiligo.  The researchers discovered that NALP1, a gene that controls the part of the immune system that serves to alert the body to viral and bacterial attacks, is a key gene involved in predisposing to vitiligo and all the other autoimmune diseases that affected these families.

This gene is a very common “genetic risk factor” for many people and having this genetic variation increases the risk of disease about two-to-four-fold.  As Richard Spritz, Director of the Human Medical Genetics Program at UCDHSC and lead investigator for this study says, “What’s really exciting for us is that NALP1 hasn’t been specifically implicated in autoimmune diseases before.  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.”

Dr Spritz and his team have been fortunate to receive a large grant which they have used to work with clinicians all around the world to recruit more patients and continue the genetics research with an even more powerful technique called a GWAS (Genome-wide Association Study), with the aim of finding all the rest of the genes that have any significant effect on vitiligo susceptibility.  This approach uses SNPs, single nucleotide polymorphisms, which are places in the human DNA sequence where some people are known to have one single DNA base (say G), whereas others have a different base (say T).  DNA of the volunteers gets analysed robotically for 370,000 different SNPs throughout the chromosomes.  By comparing the SNPs in thousands of people with Vitiligo and thousands without, and feeding it all into a computer, it is possible to find clusters of SNPs next to each other that are significantly associated with vitiligo.  These show where the important genes are.

Dr. Spritz and his team hope soon to be 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 will also be found to be involved in autoimmune and autoinflammatory diseases such as Type 1 diabetes, Addison’s disease, thyroid disease and lupus.  As Spritz concludes:

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.”

Dr Richard Spritz and British collaborator Prof Dot Bennett thank everyone who has supported, funded and participated in this research in particular the patients, the researchers and the hospitals involved, without whom, this research would not be possible.