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Published on: March 8, 2024
Skin tape proteomics identifies pathways associated with transepidermal water loss and allergen polysensitization in
Elena Goleva1, Agustin Calatroni2, Petra LeBeau2
1Department of Pediatrics, National Jewish Health, Denver, Colo.
Insights
Skin tape strip (STS) analysis identified a unique protein signature in children with atopic dermatitis (AD) and food allergy (FA). This signature, linked to skin barrier dysfunction, persists into adulthood, suggesting a specific endotype for AD with FA.
Area of Science:
- Dermatology
- Allergology
- Proteomics
Background:
- Atopic dermatitis (AD) and food allergy (FA) are frequently co-occurring conditions.
- Skin barrier dysfunction is a hallmark of AD and a potential pathway for allergen sensitization.
- Novel biomarkers are crucial for evaluating interventions targeting skin barrier defects in AD and FA.
Purpose of the Study:
- To identify skin biomarkers in nonlesional skin of children with AD and FA.
- To investigate the association between skin proteomic profiles and clinical phenotypes of AD and FA.
- To validate identified biomarkers in an independent adult cohort.
Main Methods:
- Collected skin tape strip (STS) samples from nonlesional skin of children with AD and FA, AD without FA, and nonatopic controls.
- Performed mass spectrometry-based proteomic analysis on STS samples.
- Assessed transepidermal water loss (TEWL) and allergic sensitization.
- Validated proteomic findings in an independent cohort of adult AD patients with and without FA.
Main Results:
- Identified a distinct cluster of 45 proteins (PC1) highly expressed in STS from children with AD and FA.
- PC1 proteins correlated significantly with TEWL and allergic sensitization.
- PC1 proteins included keratin intermediate filaments, inflammatory mediators (S100 proteins, alarmins), and metabolic enzymes.
- Differential expression of PC1 proteins was confirmed in adult AD patients with a history of peanut allergy.
Conclusions:
- Discovered a unique STS proteomic endotype in children with AD and FA, characterized by PC1 proteins.
- This endotype appears to persist into adulthood, suggesting a stable molecular signature.
- PC1 proteins are implicated in skin barrier abnormalities and may contribute to epicutaneous sensitization to food allergens.
Background:
Atopic dermatitis (AD) and food allergy (FA) are associated with skin barrier dysfunction.
Objective:
Skin biomarkers are needed for skin barrier interventions studies.
Methods:
In this study, skin tape strip (STS) samples were collected from nonlesional skin of 62 children in AD FA+, AD FA-, and nonatopic groups for mass spectrometry proteomic analysis. transepidermal water loss and allergic sensitization were assessed. STS proteomic analysis results were validated in an independent cohort of 41 adults with AD with and without FA versus nonatopic controls.
Results:
A group of 45 proteins was identified as a principal component 1 (PC1) with the highest expression in AD FA+ STSs. This novel set of STS proteins was highly correlative to skin transepidermal water loss and allergic sensitization. PC1 proteins included keratin intermediate filaments; proteins associated with inflammatory responses (S100 proteins, alarmins, protease inhibitors); and glycolysis and antioxidant defense enzymes. Analysis of PC1 proteins expression in an independent adult AD cohort validated differential expression of STS PC1 proteins in the skin of adult patients with AD with the history of clinical reactions to peanut.
Conclusions:
STS analysis of nonlesional skin of AD children identified a cluster of proteins with the highest expression in AD FA+ children. The differential expression of STS PC1 proteins was confirmed in a replicate cohort of adult AD patients with FA to peanut, suggesting a unique STS proteomic endotype for AD FA+ that persists into adulthood. Collectively, PC1 proteins are associated with abnormalities in skin barrier integrity and may increase the risk of epicutaneous sensitization to food allergens.
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