Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:135

Article

da Rosa, Joel Correa¹  Malajian, Dana^2,3  Shemer, Avner⁴  Rozenblit, Mariya^1,2,5  Dhingra, Nikhil^2,5,6  Czarnowicki, Tali^1,2  Khattri, Saakshi²  Ungar, Benjamin^1,2,5  Finney, Robert^2,7  Xu, Hui¹  Zheng, Xiuzhong¹  Estrada, Yeriel D.¹  Peng, Xiangyu^1,5  Suarez-Farinas, Mayte^1,2  Krueger, James G.^1,2  Guttman-Yassky, Emma^2,5 

[1] Rockefeller Univ, Ctr Clin & Translat Sci, New York, NY 10021 USA

[2] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA

[3] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA

[4] Tel Hashomer, Dept Dermatol, Tel Aviv, Israel

[5] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[6] North Shore Long Isl Jewish Hosp, Dept Med, Manhasset, NY USA

[7] Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol, Philadelphia, PA 19107 USA

关键词: Atopic dermatitis;    allergic contact dermatitis;    patch testing;    T-cell polarization;    human skin;    nickel;    rubber;    fragrance;   

DOI  :  10.1016/j.jaci.2014.11.017

来源: Elsevier

【 摘 要 】

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, T(H)1-subset, and T(H)2-subset genes in nickel-related AD responses, with increasedT(H)17/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 T(H)1 products, some increases in levels of T(H)17 products, and inconsistent upregulation in levels of T(H)2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased T(H)2, T(H)17, and negative regulator levels compared with those seen in non-AD skin.

【 授权许可】

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