Genome-wide association study in alopecia areata implicates both innate and adaptive immunity

Lynn Petukhova, Madeleine Duvic, Maria Hordinsky, David Norris, Vera Price, Yutaka Shimomura, Hyunmi Kim, Pallavi Singh, Annette Lee, Wei V. Chen, Katja C. Meyer, Ralf Paus, Colin A.B. Jahoda, Christopher I. Amos, Peter K. Gregersen, Angela M. Christiano

287 Citations (Scopus)


Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P≥ 5 × 10-7). Here we show an association with genomic regions containing several genes controlling the activation and proliferation of regulatory T cells (Treg cells), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), interleukin (IL)-2/IL-21, IL-2 receptor A (IL-2RA; CD25) and Eos (also known as Ikaros family zinc finger 4; IKZF4), as well as the human leukocyte antigen (HLA) region. We also find association evidence for regions containing genes expressed in the hair follicle itself (PRDX5 and STX17). A region of strong association resides within the ULBP (cytomegalovirus UL16-binding protein) gene cluster on chromosome 6q25.1, encoding activating ligands of the natural killer cell receptor NKG2D that have not previously been implicated in an autoimmune disease. By probing the role of ULBP3 in disease pathogenesis, we also show that its expression in lesional scalp from patients with AA is markedly upregulated in the hair follicle dermal sheath during active disease. This study provides evidence for the involvement of both innate and acquired immunity in the pathogenesis of AA. We have defined the genetic underpinnings of AA, placing it within the context of shared pathways among autoimmune diseases, and implicating a novel disease mechanism, the upregulation of ULBP ligands, in triggering autoimmunity.

Original languageEnglish
Issue number7302
Pages (from-to)113-117
Number of pages5
Publication statusPublished - 01.07.2010


Dive into the research topics of 'Genome-wide association study in alopecia areata implicates both innate and adaptive immunity'. Together they form a unique fingerprint.

Cite this