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 © 2010 Macmillan Publishers Limited. All rights reservedCorrespondence and requests for materials should be, addressed to A.M.C. (amc65@columbia.edu). Supplementary Information is linked to the online version of the paper at www.nature.com/nature.Author Contributions L.P. performed technical aspects in preparation of samples for genotyping, the statistical analysis and preparation of the manuscript. M.D., V.P., M.H. and D.N. participated in phenotyping, diagnosis, and access to patient samples from the National Alopecia Areata Registry. Y.S., P.S. and H.K. provided expertise in RT-PCR and immunofluorescence. K.C.M. and R.P. provided expertise in immunhistochemistry. A.L. and P.K.G. provided control samples and performed genotyping as well as insight into autoimmune diseases. W.V.C. and C.I.A. provided additional statistical analysis and control samples from a distinct cohort. C.A.B.J. performed hair follicle microdissection and provided indispensable scientific expertise on the dermal sheath. A.M.C. provided oversight and conceptual guidance to the project, input into the functional significance of candidate genes, supervision of laboratory personnel, management of collaborations, preparation of the manuscript and all reporting requirements for granting agencies.Reprints and permissions information is available at www.nature.com/reprints.The authors declare no competing financial interests.Readers are welcome to comment on the online version of this article at www.nature.com/nature. NIH Public Access Author ManuscriptNature. Author manuscript; available in PMC 2011 January 1. 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.AA affects about 5.3 million people in the United States alone, including males and females across all ethnic groups, with a lifetime risk ...

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In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/ or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins.Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 1541% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested.These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fce-receptor bearing cells armed with the relevant IgE antitoxin. (J. Clin. Invest. 1993Invest. . 92:1374Invest. -1380

Interleukin-1␤ (IL-1␤

Background: Analyzing apoptosis has been an integral component of many biological studies. However, currently available methods for quantifying apoptosis have various limitations including multiple, sometimes cell-damaging steps, the inability to quantify live, necrotic and apoptotic cells at the same time, and non-specific detection (i.e. "false positive"). To overcome the shortcomings of current methods that quantify apoptosis in vitro and to take advantage of the 96-well plate format, we present here a modified ethidium bromide and acridine orange (EB/AO) staining assay, which may be performed entirely in a 96-well plate. Our method combines the advantages of the 96-well format and the conventional EB/AO method for apoptotic quantification.