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Growing up with atopic dermatitis: transitions toward the adult molecular profile

Published online: January 13, 2021

Atopic dermatitis (AD) is a common inflammatory skin disorder that begins during the first five years of life in 90% of affected individuals and can be lifelong. Understanding of the pathogenesis of AD has largely been based on analysis of the inflamed skin of affected adults and has demonstrated TH2 immune skewing. This understanding contributed to the development of the first monoclonal antibody for treatment of AD, designed to suppress TH2 immune activation and currently approved for moderate-to-severe AD as young as 6 years of age.

Recent molecular profiling studies have demonstrated that infants and toddlers with the recent onset of AD also have TH2 skewing in skin, but display differences from adults in other immune biomarkers. In a recent article published in The Journal of Allergy and Clinical Immunology (JACI), using RNA-Sequencing, Renert-Yuval et al. have now examined the gene expression patterns of lesional and nonlesional biopsied skin from 54 affected individuals of various ages, including children under 5 years, school-aged children, adolescents, and adults, to examine shared patterns and differences.

Skewing towards TH2 immunity, but also TH22 (interleukin (IL)-22), was shared across all ages and correlated with disease severity, highlighting the central role of these pathways in the pathogenesis of AD. In contrast, TH1 polarization with increases in interferon-gamma and CXCL9/10/11 was confined to adult lesional skin, whereas increases in IL-9, IL-33, and the IL-33 receptor, which have been linked to early mite sensitization, food allergies and asthma, were only noted in infants. Reductions in the expression of genes encoding tight junction proteins and lipid-modifying enzymes that are important for the epidermal barrier were also shared across the ages, but down-regulation of many terminal different proteins of the barrier, including filaggrin, was specific to adult skin.

These findings support the ongoing development of new therapeutic agents that target the TH2 and possibly the TH22 pathway. However, the data also highlight that AD lesional and nonlesional skin of pediatric patients, including adolescents, differs from that of adults, and indicate age-specific patterns in immune and epidermal barrier biomarkers that may affect outcome and therapeutic responses.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.