Mild atopic dermatitis lacks systemic inflammation, and shows reduced non-lesional skin abnormalities

Mild atopic dermatitis lacks systemic inflammation, and shows reduced non-lesional skin abnormalities:



Publication date: Available online 1 October 2020

Source: Journal of Allergy and Clinical Immunology

Author(s): Helen He, Ester Del Duca, Aisleen Diaz, Hyun Je Kim, Jesús Gay-Mimbrera, Ning Zhang, Jianni Wu, Jessica Beaziz, Yeriel Estrada, James G. Krueger, Ana B. Pavel, Juan Ruano, Emma Guttman-Yassky

Abstract

Background

Molecular studies in atopic dermatitis (AD) are largely restricted to patients with moderate-to-severe disease.

Objective

To evaluate skin and blood abnormalities in mild, moderate, and severe AD.

Methods

Skin and blood samples were obtained from 61 AD patients (20 mild/limited, 17 moderate, 24 severe) and 20 healthy subjects. Immune and barrier markers were measured in lesional, non-lesional, and healthy skin by qRT-PCR and immunohistochemistry, and in blood using the OLINK proteomic assay.

Results

Cellular markers of epidermal hyperplasia and T-cell/dendritic cell infiltration were increased in AD tissues of all severity patient groups versus controls, while downstream TH2, TH22, TH1, TH17-related mediators demonstrated incremental elevations with increasing disease severity, in both lesional and non-lesional skin. While TH2 (IL13, CCL17, CCL26) and TH22 (IL-22) cytokines were significantly elevated in both AD lesional and non-lesional skin of all patients regardless of severity, mild/limited AD patients showed increases in TH1 (IFNG, CXCL9, CXCL10) and TH17 (IL-17A, CCL20, CXCL1) markers in lesional, but not non-lesional skin. Treg-related mediators (IL-10, FOXP3) were comparably up-regulated in all groups, without displaying the severity-based gradient in other immune axes. Unsupervised clustering aligned samples along a severity spectrum, where non-lesional mild/limited AD skin clustered with healthy controls. Furthermore, while the blood profiles of moderate and severe AD patients showed gradual increases in TH1/TH2/TH17-related and atherosclerosis/cardiovascular risk (CCL7, FGF21, IGFBP1) proteins, mild/limited AD lacked significant differences versus controls.

Conclusion

Mild/limited AD shows high TH2/TH22 activation primarily localized to skin lesions, and lacks the systemic inflammation of moderate and severe disease.

Graphical abstract

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