Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin - 05/03/15
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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, allergic contact dermatitis, patch testing, T-cell polarization, human skin, nickel, rubber, fragrance
Abbreviations used : ACD, AD, DC, DEG, DNCB, FCH, FLG, FoxP3, IHC, IL1F10, LC, MMP, RT-PCR
Plan
| J.C.R., J.G.K., M.S.-F., M.R., T.C., N.D., and B.U. were supported by grant no. 5UL1RR024143-02 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. E.G.-Y. was supported by the Dermatology Foundation Physician Scientist Career Development Award and by a CTSA grant from Rockefeller University (UL1 TR000043). D.M. was supported by the American Dermatological Association's Medical Student Fellowship. |
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| Disclosure of potential conflict of interest: J. G. Krueger has received grants paid to his institution and personal fees from Novartis, Pfizer, Janssen, Lilly, Merck, Kadmon, Dermira, Boehringer, BMS, and Paraxel during the conduct of the study; has received grants paid to his institution from Amgen, Innovaderm, and Kyowa; and has received personal fees from Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Xenoport, and Kineta. E. Guttman-Yassky is a board member for Sanofi-Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, and Leo Pharma; has consultant arrangements with Regeneron, Sanofi Aventis, MedImmune, Celgene, Steifel/GlaxoSmithKline, Celsus, BMS, Amgen, and Drais; and has received research support from Regeneron, Celgene, BMS, and Janssen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 3
P. 712-720 - mars 2015 Retour au numéro
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