title: Vaccinia virus-specific molecular signature in atopic dermatitis skin.
abstract: BACKGROUND
  Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown.
  
  
  OBJECTIVE
  Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV.
  
  
  METHODS
  Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline.
  
  
  RESULTS
  Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B(4) receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity.
  
  
  CONCLUSIONS
  This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
authors.forename: Tonya N
authors.initials: TN
authors.lastname: Watkins
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D003876:Dermatitis, Atopic / Q000150:complications / Q000503:physiopathology / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007617:Kaposi Varicelliform Eruption / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity*; D055815:Young Adult
chemical_list: D011506:Proteins