Joel Correa da Rosa1, Dana Malajian2, Avner Shemer3, Mariya Rozenblit4, Nikhil Dhingra5, Tali Czarnowicki6, Saakshi Khattri7, Benjamin Ungar4, Robert Finney8, Hui Xu1, Xiuzhong Zheng1, Yeriel D Estrada1, Xiangyu Peng9, Mayte Suárez-Fariñas6, James G Krueger6, Emma Guttman-Yassky10. 1. Center for Clinical and Translational Science, Rockefeller University, New York, NY. 2. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY. 3. Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel. 4. 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. 5. 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. 6. Center for Clinical and Translational Science, Rockefeller University, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. 7. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. 8. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Jefferson Medical College, Philadelphia, Pa. 9. Center for Clinical and Translational Science, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. 10. 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.
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.
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: Lisa J Martin; Hua He; Margaret H Collins; J Pablo Abonia; Joceyln M Biagini Myers; Michael Eby; Hanna Johansson; Leah C Kottyan; Gurjit K Khurana Hershey; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2017-11-10 Impact factor: 10.793
Authors: Kilian Eyerich; Sara J Brown; Bethany E Perez White; Reiko J Tanaka; Robert Bissonette; Sandipan Dhar; Thomas Bieber; Dirk J Hijnen; Emma Guttman-Yassky; Alan Irvine; Jacob P Thyssen; Christian Vestergaard; Thomas Werfel; Andreas Wollenberg; Amy S Paller; Nick J Reynolds Journal: J Allergy Clin Immunol Date: 2018-11-07 Impact factor: 10.793
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Authors: David A Ewald; Dana Malajian; James G Krueger; Christopher T Workman; Tianjiao Wang; Suyan Tian; Thomas Litman; Emma Guttman-Yassky; Mayte Suárez-Fariñas Journal: BMC Med Genomics Date: 2015-10-12 Impact factor: 3.063