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A New Gene Linked to Vitiligo and Susceptibility to Autoimmune Disorders

These results point to a link between vitiligo and the innate immune system.

Patients with vitiligo have an increased risk for developing such other autoimmune and autoinflammatory diseases as autoimmune thyroiditis, pernicious anemia, Addison disease, type 1 diabetes, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus. Family members are frequently affected by these same diseases, implicating a genetic factor in their causation. Investigators at the University of Colorado had previously found that vitiligo with an associated susceptibility to multiple autoimmune and autoinflammatory diseases mapped to a locus on chromosome 17p13; no such linkage was present in patients who had vitiligo alone. The same investigators recently employed detailed genotypic analyses using single nucleotide polymorphisms (SNPs) to identify a gene associated with the combined vitiligo/autoimmune and autoinflammatory susceptibility.

Initial experiments indicated that polymorphisms located in the coding or promoter region of the NALP1 gene were responsible for disease susceptibility. NALP1 encodes a protein that is involved in regulation of innate immune responses, that is expressed at high levels in T-lymphocytes and Langerhans cells, and that activates the proinflammatory cytokine IL-1ß. Examination of 114 families affected by this group of diseases identified at least two independent NALP1 variants closely associated with susceptibility.

Comment: This landmark study identifies a gene associated with at least some forms of vitiligo, providing evidence of the involvement of the innate immune system in the pathogenesis of this disease. The role of the innate immune system in conditions such as acne, leprosy, and atopic dermatitis has generated intense interest, and vitiligo can now be added to the list. At least as important is the possibility raised by these findings of discovering new therapeutic agents. For example, if the variant NALP1 protein synthesized in vitiligo/autoimmune and inflammatory disease excessively activates the immune system, then administration of selective inhibitors of this protein may produce repigmentation of the vitiligo.

— Craig A. Elmets, MD

Published in Journal Watch Dermatology March 30, 2007


Jin Y et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007 Mar 22; 356:1216-25.




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