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Untargeted proteomics highlights interaction between barrier dysfunction and immune dysregulation as key pathways in Atopic Dermatitis in Children
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  • Sean Wee,
  • Anna de Beer,
  • Hiromi Koh,
  • Jocelyn Ong,
  • Jing Hui Low,
  • Yan Ting Lim,
  • Shi Mei Wang,
  • Radoslaw Sobota M,
  • Elena Goleva,
  • Donald Leung,
  • Wen Chin Chiang,
  • Mei Chien Chua,
  • Anand Andiappan
Sean Wee
Singapore Immunology Network
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Anna de Beer
Singapore Immunology Network
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Hiromi Koh
Institute of Molecular and Cell Biology
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Jocelyn Ong
Singapore Immunology Network
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Jing Hui Low
Singapore Immunology Network
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Yan Ting Lim
Institute of Molecular and Cell Biology
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Shi Mei Wang
Institute of Molecular and Cell Biology
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Radoslaw Sobota M
Institute of Molecular and Cell Biology
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Elena Goleva
National Jewish Health South Denver
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Donald Leung
National Jewish Health South Denver
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Wen Chin Chiang
KK Women's and Children's Hospital Children's Services
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Mei Chien Chua
KK Women's and Children's Hospital
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Anand Andiappan
Singapore Immunology Network

Corresponding Author:anand_andiappan@immunol.a-star.edu.sg

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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.