Untargeted proteomics highlights interaction between barrier dysfunction
and immune dysregulation as key pathways in Atopic Dermatitis in
Children
Abstract
Background: Atopic Dermatitis (AD) is a chronic condition
characterised by recurrent skin lesions and itch, significantly
impacting patients’ quality of life. AD is most common during childhood,
with global prevalence ranging between 10% and 20%.
Objective: Identifying protein biomarkers underlying AD in
children, to better understand the pathogenesis. Methods:
Cross-sectional study using untargeted tandem mass spectrometry to
analyse skin tape protein extracts from 71 10-year-old Singaporean
children. Subjects were stratified into three groups, no history of AD
(NoAD=29), history of AD but no symptoms at time of sample collection
(PastAD=22) and present AD (PresentAD=20). Significant proteins were
shortlisted and functional analyses were performed. Results:
397 differentially expressed proteins were identified
(p-value<0.05) with 18 proteins shared with a validation cohort.
Ingenuity pathway analysis shows that ‘PastAD vs PresentAD’ share common
pathways with ‘NoAD vs PresentAD’. The top pathways obtained are related
to inflammatory responses, such as neutrophil degranulation, JAK-STAT
signalling and interleukin-1 family signalling. Conclusions:
Multiple protein biomarkers and pathways, including keratinization,
inflammatory responses and oxidative stress response, are involved in
the onset and persistence of AD. Despite resolution of disease
manifestations in PastAD subjects, functional analyses show that some
pathways and biomarkers indicative of AD persist.