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Study Identifies Genes That Unleash Immune System Assault on Hair

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Scientists have discovered the genetic underpinnings of a disease that causes baldness by launching an immune system attack on hair follicles.

Alopecia areata afflicts about 5.3 million people in the United States, causing baldness in patches that sometimes spread to cover the scalp or the entire body. It's the most common cause of baldness among women.

The disease is caused by an autoimmune reaction involving T cells and human leukocyte antigen (HLA) molecules, two immune system mainstays, but the genetic basis for alopecia areata has been largely unknown. By comparing the genomes of 1,054 people with the disease and 3,278 without it in a genome-wide association study, a team of scientists that included two members of the MD Anderson faculty linked a variety of genetic variations with the disease. Their results are reported this month in the prominent scientific journal Nature.

"The genes identified are related to immunity and two, CTLA4 and HLA, are autoimmune genes," says Christopher Amos, Ph.D., professor in the Department of Epidemiology in the Division of Cancer Prevention and Population Sciences.

"One of the more interesting genes is expressed in the hair follicle, so it's probably the target of the autoimmune responses." says Amos, whose group developed the database for the project's registry and performed much of the statistical analysis required to more precisely study genomic regions associated with the disease.

Madeleine Duvic, M.D., professor in MD Anderson's Department of Dermatology, has long studied the role of HLA in alopecia areata and considered it an autoimmune disease for many years. She is principal investigator on the project's tissue and data repository, the national Alopecia Areata Registry, which is funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases.

"This project has taken 10 years and we are thrilled with the results. Knowing the genes involved will help us to develop targeted therapy," Duvic says. "I work in understanding cutaneous T cell lymphoma (CTCL) which also has loss of hair mediated by T cells, similar HLA associations and abnormal T cell signaling pathways that are relevant to alopecia areata as well as CTCL."

More than 7,890 patients have registered and over 2,800 patients have donated blood samples used study. The website that Amos and his group designed allows patients to self-register at  www.alopeciaareataregistry.org. Patients who donated samples were examined at registry sites at MD Anderson, University of California, University of Colorado, University of Minnesota or Columbia University.

The research effort was headed by Angela Christiano, Ph.D., of Columbia University, corresponding author of the Nature paper.

One quirk about alopecia areata: it is thought to be behind the phenomenon of sudden whitening of hair during times of stress, grief or fear. The immune system attack targets pigmented hair, leaving only the white hair to grow.

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