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J Am Acad Dermatol. 2019 Aug;81(2):510-519. doi: 10.1016/j.jaad.2019.04.036. Epub 2019 Apr 19.

The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

Author information

1
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
2
Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
3
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
4
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
5
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: apaller@northwestern.edu.

Abstract

BACKGROUND:

Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.

OBJECTIVE:

To analyze blood inflammatory proteins of early pediatric AD.

METHODS:

Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.

RESULTS:

In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).

LIMITATIONS:

Different baseline expression levels in healthy pediatric vs adult samples.

CONCLUSIONS:

Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.

KEYWORDS:

Atopic dermatitis; Olink; infant; multiplex assay; pediatric; peripheral blood; proximity extension assay

PMID:
31009665
DOI:
10.1016/j.jaad.2019.04.036

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