Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis

Publication date: Available online 24 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Lisa Zhou, Alexandra Leonard, Ana B. Pavel, Kunal Malik, Aishwarya Raja, Jacob Glickman, Yeriel D. Estrada, Xiangyu Peng, Ester del Duca, Juan Sanz-Cabanillas, Juan Ruano, Hui Xu, Ning Zhang, Huei-Chi Wen, Juana Gonzalez, Sandra Garcet, James G. Krueger, Emma Guttman-Yassky

Abstract

Background

Atopic dermatitis/AD shows differential clinical presentation in older compared to younger patients. Nevertheless, changes in the AD molecular profile with age are unknown.

Objective

To characterize age-related changes in the AD profile.

Methods

We evaluated age-specific changes in lesional and non-lesional tissues and blood from moderate-to-severe AD patients (n=246) and age-matched controls (n=72) using immunohistochemistry, qRT-PCR, and Singulex in a cross-sectional study. Patients were analyzed using age-groups (18-40, 41-60, and 61+ years old).

Results

While disease severity/SCORAD was similar across AD age-groups (mean:∼60; P=0.873), dendritic cell infiltrates (CD1b⁺, FcεRI⁺; P<0.05) decreased with age. T_H2 measures (IL-5, IL-13, CCL13, CCL18, CCL26) significantly decreased with age in AD, despite increasing with age in controls. Consistent with T_H2 axis decreases, serum IgE and eosinophils negatively correlated with age in AD (r=-0.24, r=-0.23, P<0.05). T_H22-secreted IL-22 also decreased with age uniquely in AD (P<0.05). T_H1- (IFN-γ, IL-12/23p40, STAT1, CXCL9; P<0.05 for CXCL9) and T_H17-related markers (IL-17A, IL-20; P<0.05 for IL-20) increased with age in both AD and controls. Terminal differentiation measures significantly increased in older AD patients (LOR, FLG; P<0.05), while S100As (S100A8; P<0.01) and hyperplasia markers (epidermal thickness/ET, K16, Ki67; P<0.05 for K16) decreased. Serum trends in AD mimicked skin findings, with T_H2 downregulation (CCL26; r=-0.32, P<0.1) and T_H1 upregulation (IFN-γ; r=0.48, P<0.01) with age.

Conclusion

The adult AD profile varies with age. While T_H1/T_H17-skewing decreases in both AD and controls, AD shows unique decreases in T_H2/T_H22 polarization, and normalization of epithelial abnormalities. Thus, age-specific treatment approaches may be beneficial for AD.

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