RESEARCH ARTICLE


Stratum Corneum Biomarkers in Atopic Dermatitis: Biological and Spatial Variability



Ruzica Jurakic Toncic1, Sanja Kezic2, Suzana Ljubojevic Hadzavdic1, Branka Marinovic1, Ivone Jakasa3, *
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1 Department of Dermatology and Venereology, University Hospital Center, Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia
2 Amsterdam UMC, Coronel Institute of Occupational Health, Amsterdam, Netherlands
3 Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Laboratory for Analytical Chemistry, Zagreb, Croatia


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Creative Commons License
© 2020 Jurakic Toncic et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Laboratory for Analytical Chemistry, Pierottijeva 6, Zagreb, Croatia; Tel: ++385-1-4605068; E-mail: ijakasa@pbf.unizg.hr


Abstract

Background:

Atopic dermatitis is a highly heterogeneous skin disease, mainly affecting children. Introduction of biological therapies has urged the development of biomarkers to facilitate personalized therapy. Stratum corneum biomarkers emerged as a promising non-invasive alternative to skin biopsy, yet validation of spatial and biological variability is essential for their application in clinical research.

Objective:

To assess spatial and biological variability of stratum corneum biomarkers for atopic dermatitis.

Methods:

Stratum corneum was collected from 17 atopic dermatitis patients by consecutive application of eight adhesive tapes to a lesional skin site and 2 cm and 4 cm from the lesion. Two non-lesional sites at a 2 cm distance from the same lesion were collected to determine biological variability. Filaggrin degradation products (NMF) were determined by liquid chromatography and thirteen cytokines (IL-4, IL-13, IL-18, IL-31, IL-33, CCL17, CCL22, CCL27, CXCL8, IL-1α, IL-RA, IL-18, IL-22) by multiplex immunoassay.

Results:

Biomarker levels showed gradual changes from lesional to non-lesional skin sites at 2 cm and 4 cm; magnitude and direction of change were biomarker-specific. Intra-subject variability ranged from 17.3% (NMF) to 85.1% (CXCL8). Biomarker levels from two stratum corneum depths were highly correlated; several biomarkers showed significant depth dependence.

Conclusion:

Stratum corneum enables non-invasive collection of relevant immune and epidermal biomarkers, but biomarker-specific spatial and biological variability emphasizes the importance of standardized procedures for stratum corneum collection.

Keywords: Atopic dermatitis, Biomarkers, Non-invasive, Cytokines, Filaggrin, Stratum corneum.