Alopecia Areata和許多autoimmune dz 有相同的SNP，這些SNP所在的gene和 immune regulation有關，AA是個autoimmune dz

The Root of the Alopecia Areata Problem

A genome-wide association study of AA reveals shared pathways with other autoimmune diseases, as well as a novel mechanism in triggering autoimmunity.

The fundamental mechanisms underlying the autoimmune attack in alopecia areata (AA) are still unknown. To tease apart the genetic causes of AA, investigators undertook a genome-wide association study (GWAS) using a sample of 1054 cases in the National Alopecia Areata Registry and 3278 controls from other studies.

The researchers found 139 single nucleotide polymorphisms that were strongly and significantly associated with AA. They found strong associations in regions linked to other autoimmune diseases — in particular, CTLA4, IL-2/IL-21, IL-2RA and genes critical to T-cell regulation — as well as a strongly associated region in the ULBP gene cluster. The ULBP gene appears to be a stress-induced molecule that serves as a danger signal to alert NK, natural killer T, {delta}{gamma}T, and CD8+ T lymphocytes. ULBP was highly upregulated in early active AA follicles (but not in normal follicles) in two patients. The researchers speculate that upregulation of ULBP3 in the dermal sheath of the hair follicle induces activation of CD8+NKG2D+ cytotoxic T cells, which are likely responsible, at least in part, for the observed hair loss in AA.

Comment: The GWASs just keep coming. This is a nice study that defines a unique disease mechanism for AA but also demonstrates a shared pathway with other autoimmune disorders, validating the "common-cause" hypothesis of autoimmune disease. The GWAS revealed several risk loci that have been implicated in rheumatoid arthritis, type I diabetes, celiac disease, systemic lupus erythematosus, multiple sclerosis, and psoriasis. The common-cause hypothesis is attractive, because it ties together many disparate autoimmune phenomena into a single, central immunologic disorder. How, when, and why select organs are targeted, and why certain autoimmune conditions favor women, are unknown. A central hypothesis raises the possibility of a coordinated search for novel therapies aimed at these phenotypically distinct conditions.

— Hensin Tsao, MD, PhD

Published in Journal Watch Dermatology August 5, 2010
Citation(s):

Petukhova L et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 2010 Jul 1; 466:113.

* Medline abstract (Free)

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