title: Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin.
abstract: BACKGROUND
  Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated.
  
  
  OBJECTIVE
  We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge.
  
  
  METHODS
  Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber).
  
  
  RESULTS
  Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD.
  
  
  CONCLUSIONS
  Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and negative regulator levels compared with those seen in non-AD skin.
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY.
authors.forename: Joel
authors.initials: J
authors.lastname: Correa da Rosa
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Dana
authors.initials: D
authors.lastname: Malajian
authors.affiliation: Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel.
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Mariya
authors.initials: M
authors.lastname: Rozenblit
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Medicine, North Shore-Long Island Jewish Hospital, Manhasset, NY.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Dhingra
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Tali
authors.initials: T
authors.lastname: Czarnowicki
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Saakshi
authors.initials: S
authors.lastname: Khattri
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Jefferson Medical College, Philadelphia, Pa.
authors.forename: Robert
authors.initials: R
authors.lastname: Finney
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY.
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY.
authors.forename: Yeriel D
authors.initials: YD
authors.lastname: Estrada
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Peng
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: eguttman@rockefeller.edu.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D040502:Calgranulin B / Q000235:genetics / Q000276:immunology; D003358:Cosmetics / Q000737:chemistry; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007840:Latex / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000276:immunology; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009532:Nickel / Q000276:immunology; D010328:Patch Tests; D012408:Rubber / Q000737:chemistry; D012867:Skin; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D059467:Transcriptome / Q000276:immunology*
chemical_list: D000485:Allergens; D040502:Calgranulin B; D003358:Cosmetics; D016207:Cytokines; D007840:Latex; D009532:Nickel; D012408:Rubber; D053508:Matrix Metalloproteinase 12; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Atopic dermatitis; T-cell polarization; allergic contact dermatitis; fragrance; human skin; nickel; patch testing; rubber