Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Abstract

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized by skin and systemic inflammation, and barrier dysfunction. Herein, we investigate the proteomic profile of AD skin barrier to identify a unique signature with an easy‐performed sampling approach. We enrolled 8 moderate‐to‐severe AD patients and 8 age‐ and gender‐matched healthy controls. Swabs were obtained from non‐lesional skin of retroauricular area and antecubital fold. Peptide mixtures obtained through protein precipitation and in‐solution digestion were analysed using NanoLC‐MS/MS. Label‐free quantification and statistical analysis were conducted in MaxQuant and Perseus. Bioinformatics analysis was performed using Gene Ontology and STRING. We identified 908 proteins and 35 differentially expressed proteins were selected (fold change 2, FDR < 0.05). Particularly, AD skin showed downregulation of skin hydration factors, structural and epidermal proteins, abnormalities in protease‐proteasome complex and lipid metabolism profile. Imbalance of antioxidant and inflammatory processes, along with TDRD15 upregulation was also observed. Our result showed partial overlap with skin biopsy/tape‐strips studies, showing the reliability of our sampling approach which could be an easier method of detection of hallmark barrier proteins in AD. Furthermore, we displayed a new differentially expressed set of proteins, not yet explored in AD which can have a potential role in AD pathomechanisms.

Identification of Immunological Biomarkers of Atopic Dermatitis by Integrated Analysis to Determine Molecular Targets for Diagnosis and Therapy

“…AD is characterized by impaired skin barrier and chronic inflammation. 36 MMP-9, as broad-spectrum protease, can break down a range of matrix and other proteins, causing substantial tissue damage and barrier dysfunction of AD pathology. 37 Elevated level of CCR5 in AD induced chronic inflammation, impairing the skin of AD.…”

Recent progress at the psoriasis and atopic dermatitis research front: An experimental dermatology perspective

“…Proteomic analysis of skin swabs obtained from AD patients or healthy controls further enriches the diagnostic toolbox. This method has identified 35 differentially expressed proteins, including skin hydration factors, structural proteins and lipid metabolism, which were downregulated, and inflammatory process‐related and antioxidant imbalance proteins that were upregulated in AD 10 . This study establishes an easily performed sampling approach for proteomic studies to identify potential biomarkers for AD.…”

“…We also include new EXD studies related to allergic contact dermatitis (ACD), because it shares similar signs and symptoms as AD, including pruritus, along with burning and stinging 8 . In this Editorial, these recent EXD papers are briefly highlighted and placed into the context of the current literature, including four articles in the current issue 9‐12 . With this exercise, the Editors hope to synthesize exemplarily where translational immunopathology research in these key areas of experimental dermatology is headed, and which challenges and open questions remain.…”

Regulatory T Cells Exhibit Interleukin-33-Dependent Migratory Behavior during Skin Barrier Disruption

“…The skin is an important barrier that protects against invasion by foreign substances, including harmful microorganisms and irritants, and retains water in the body [ 1 , 2 ]. Several dermatological conditions, including atopic dermatitis (AD), are associated with dry skin resulting from skin barrier disruption [ 3 , 4 ]. Indeed, downregulation of skin hydration factors such as natural moisturizing factors (NMFs) and molecules indispensable to skin barrier homeostasis, vinculin and late cornified envelope 2A are found in skins of AD patients [ 4 ].…”