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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

Zhou, Lisa¹  Leonard, Alexandra¹  Pavel, Ana B.¹  Malik, Kunal¹  Raja, Aishwarya¹  Glickman, Jacob¹  Estrada, Yeriel D.¹  Peng, Xiangyu¹  del Duca, Ester¹  Sanz-Cabanillas, Juan²  Ruano, Juan²  Xu, Hui¹  Zhang, Ning¹  Wen, Huei-Chi¹  Gonzalez, Juana³  Garcet, Sandra³  Krueger, James G.³  Guttman-Yassky, Emma¹ 

[1] Icahn Sch Med Mt Sinai, Dept Dermatol, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[2] Reina Sofia Univ Hosp, Dept Dermatol, Cordoba, Spain

[3] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA

关键词: Atopic dermatitis;    biomarker;    T(H)1;    T(H)2;    T(H)17;    T(H)22;    hyperplasia;    loricrin;    filaggrin;    aging;    skin;   

DOI  :  10.1016/j.jaci.2019.01.015

来源: Elsevier

【 摘 要 】

Background: Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. Objective: We sought to characterize age-related changes in the AD profile. Methods: We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and >= 61 years). Results: Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b(+) and Fc epsilon RI+, P < .05) decreased with age. T(H)2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T(H)2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T(H)22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T(H)1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T(H)17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T(H)2 downregulation (CCL26; r = 0.32, P < .1) and T(H)1 upregulation (IFN-gamma; r = 0.48, P < .01) with age. Conclusion: The adult AD profile varies with age. Although T(H)1/T(H)17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T(H)2/T(H)22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.

【 授权许可】

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