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Observational Study
. 2023 May;88(5):1083-1093.
doi: 10.1016/j.jaad.2022.12.050. Epub 2023 Feb 10.

Proteomic characterization of atopic dermatitis blood from infancy to adulthood

Ester Del Duca  1 , Yael Renert-Yuval  2 , Ana B Pavel  3 , Daniela Mikhaylov  4 , Jianni Wu  4 , Rachel Lefferdink  5 , Milie Fang  5 , Anjani Sheth  5 , Alli Blumstein  5 , Paola Facheris  6 , Yeriel D Estrada  4 , Stephanie M Rangel  5 , James G Krueger  2 , Amy S Paller  7 , Emma Guttman-Yassky  8
Affiliations
Observational Study

Proteomic characterization of atopic dermatitis blood from infancy to adulthood

Ester Del Duca et al. J Am Acad Dermatol. 2023 May.

Abstract

Background: Patients with atopic dermatitis (AD) have systemic biomarker dysregulation that differs by age group; however, the proteomic characteristics of these age-based changes are unknown.

Objective: To profile blood proteins of patients with AD across different age groups versus age-appropriate controls.

Methods: Using the Olink high-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (age, 0-5 years), 39 children (age, 6-11 years), 21 adolescents (age, 12-17 years), and 20 adults (age, ≥18 years) with moderate-to-severe AD and 83 age-appropriate controls.

Results: Each group presented a distinct systemic proteomic signature. Th2-related proteins were increased in infant AD and further intensified with age through adolescence and adulthood (interleukin 4/CCL13/CCL17). In contrast, Th1 axis down-regulation was detected in infants with AD and gradually reversed to increased Th1 products (interferon γ/CXCL9/CXCL10/CCL2) in patients with AD from childhood to adulthood. Despite their short disease duration, infants already had evidence of systemic inflammation, with significant upregulation of innate immunity (interleukin 17C/ interleukin-1RN), T-cell activation/migration (CCL19), Th2 (CCL13/CCL17), and Th17 (PI3) proteins. Adults with AD present unique upregulation of cardiovascular proteins related to coagulation and diabetes.

Limitations: Cross-sectional observational study with a single time point.

Conclusion: Systemic immune signatures of AD are age-specific beyond the shared Th2 immune activation. These data advocate for precision medicine approaches based on age-specific AD profiles.

Keywords: Olink; atopic dermatitis; pediatric; proteomic.

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Conflict of interest statement

Conflicts of interest Dr Guttman-Yassky is an employee of Mount Sinai; has received research funds (grants paid to the institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB; and is a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Dr Krueger has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. Dr Paller has received research funds (grants paid to the institution) from AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, KrystalBio, Regeneron, and UCB and is a consultant for AbbVie, Abeona, Acrotech, Almirall, Amgen, Amryt, Arcutis, Arena, Azitra, BioCryst, BiomX, Bridgebio, Bristol Myers Squibb, Castle Biosciences, Catawba, Eli Lilly, Exicure, Galderma, Kamari, Leo, Novan, Novartis, OM Pharma, Pfizer, Pierre Fabre, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, and UCB. Dr Rangel has received research funds (grants paid to the institution) from AbbVie, DermTech, and Galderma. Drs Del Duca, Renert-Yuval, Pavel, Wu, Lefferdink, Fang, and Facheris and authors Mikhaylov, Sheth, Blumstein, and Estrada have no conflicts of interest to disclose.

Figures

Fig 1.
Fig 1.
Comparison of differentially expressed immune-related proteins in the blood of patients with atopic dermatitis of different age groups. Heatmap of immune signaling proteins that are differentially expressed in the blood of different AD age groups, using criteria of fold change (FCH) ≥ |1.2| and P < .05. Proteins are ordered by unsupervised hierarchical clustering. The columns of the table on the right show FCH by AD age groups vs age-matched controls, and FCH across normalized groups. +P < .10, ∗P < .05, ∗∗P < .01. AD, atopic dermatitis; Adol, adolescent; N, normal.
Fig 2.
Fig 2.
Comparison of differentially expressed cardiovascular/atherosclerosis-related proteins in the blood of patients with atopic dermatitis of different age groups. Heatmap of cardiovascular/atherosclerosis signaling proteins that are differentially expressed in the blood of different AD age groups, using criteria of fold change (FCH) ≥ |1.2| and P < .05. Proteins are ordered by unsupervised hierarchical clustering. The columns of the table on the right show FCH by AD age groups vs age-matched controls, and FCH across normalized groups. +P < .10, ∗ P < .05, ∗∗ P < .01. AD, atopic dermatitis; Adol, adolescent; N, normal.
Fig 3.
Fig 3.
Pathway analysis. Common/most enriched pathways in atopic dermatitis age groups versus age-appropriate controls using differentially expressed proteins in atopic dermatitis blood versus healthy control serum by age groups analyzed with publicly available function-based pathway databases (using canonical/KEGG/Reactome/BioCarta pathways), performed with XGR software. The dashed line denotes the significance threshold (FDR < 0.05).
See this image and copyright information in PMC

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