Age-specific treatment modalities may be more beneficial for patients with atopic dermatitis (AD) across the life span, according to research that explored changes in the molecular profiles of people with moderate to severe AD. The findings were published in the Journal of Allergy and Clinical Immunology.
Researchers examined age-specific changes in blood and lesional/non-lesional tissues from patients with moderate to severe AD (n=246) and age-matched, healthy controls (n=72) via Singulex, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. Participants were categorized into 18-40, 41-60, and 61+ age groups for analysis.
Although disease severity, as measured by SCORing Atopic Dermatitis (SCORAD), was similar across the age groups with AD (mean: ∼60; P =.873), dendritic cell infiltrates (CD1b+, FcεRI+; P <.05) decreased with age. Measures of TH2 (IL-5, IL-13, CCL13, CCL18, CCL26) decreased significantly with age in participants with AD, but increased with age in controls. TH22-secreted IL-22 also decreased with age in participants with AD only (P <.05), while TH1- (IFN-γ, IL-12/23p40, STAT1, CXCL9; P <.05 for CXCL9) and TH17-related markers (IL-17A, IL-20; P <.05 for IL-20) increased with age in both controls and patients with AD.
Significant increases in terminal differentiation measures were observed in older participants with AD (LOR, FLG; P <.05), while decreases were observed in hyperplasia markers (epidermal thickness, K16, Ki67; P <.05 for K16) and S100As (S100A8; P <.01). Serum trends among participants with AD mimicked skin findings, with age-related TH2 downregulation (CCL26; r=-0.32, P <.1) and TH1 upregulation (IFN-γ; r=0.48, P <.01).
Study investigators concluded that these findings indicate age-specific treatment approaches would likely benefit patients with AD. “Therapeutic targeting with TH2-, TH22-, and TH17/TH1-specific antagonists are needed in order to understand the varying pathogenic roles of these axes in [atopic dermatitis]. Elucidating the differential patterns of immune skewing and barrier abnormalities among different [atopic dermatitis] phenotypes may be useful for developing personalized treatment approaches, especially in patients with recalcitrant [atopic dermatitis].”
Disclosures: Study authors disclose consulting fees and research funds received from Abbvie, Amgen, Anacor, AnaptysBio, Asana, Aventis, Baxter, BiogenIdec, Boehringer, Celgene, Dermira, Eli Lilly, Glenmark, Galderma, Innovaderm, Janssen, Kadmon, Kyowa, Leo Pharma, Mitsubishi Tanabe, Medimmune/Astra Zeneca, Novartis, Paraxel, Pfizer, Promius, Regeneron, Sanofi, Serono, Stiefel/GlaxoSmithKline, UCB, Vitae, and Xenoport.
Zhou L, Leonard A, Pavel AB, et al. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis [published online January 24, 2019]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2019.01.015