斑禿是一種常見自體免疫疾病,，因毛囊“免疫豁免”的喪失而引起毀容性脫發(fā),。這種病的遺傳基礎基本不清楚。現在,，對這一病癥所做的全基因組關聯研究識別出了斑禿的幾個易感位點,，其中大多數聚集在8個基因組區(qū)域,。受影響的基因活動譜表明,，這種狀況獲得性和先天性免疫可能都涉及其中,。
比較重要的關聯包括編碼天然殺手細胞受體NKG2D的激發(fā)配體的ULBP基因，它們以前沒有被與自體免疫疾病聯系起來,。 (生物谷Bioon.net)
生物谷推薦原文出處：
Nature doi:10.1038/nature09114
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
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 attack1, 2. 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.
