TY - JOUR
T1 - Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin
AU - Correa Da Rosa, Joel
AU - Malajian, Dana
AU - Shemer, Avner
AU - Rozenblit, Mariya
AU - Dhingra, Nikhil
AU - Czarnowicki, Tali
AU - Khattri, Saakshi
AU - Ungar, Benjamin
AU - Finney, Robert
AU - Xu, Hui
AU - Zheng, Xiuzhong
AU - Estrada, Yeriel D.
AU - Peng, Xiangyu
AU - Suárez-Fariñas, Mayte
AU - Krueger, James G.
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2014 American Academy of Allergy, Asthma & Immunology.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Atopic dermatitis
KW - T-cell polarization
KW - allergic contact dermatitis
KW - fragrance
KW - human skin
KW - nickel
KW - patch testing
KW - rubber
UR - http://www.scopus.com/inward/record.url?scp=84924601251&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2014.11.017
DO - 10.1016/j.jaci.2014.11.017
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 25583101
AN - SCOPUS:84924601251
SN - 0091-6749
VL - 135
SP - 712
EP - 720
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -
