Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity
Open accessAbstract
BACKGROUND: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. METHODS: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. RESULTS: The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease. CONCLUSION: Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.
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FDPs including PCA and UCA reflect the level of FLG in the skin.
“STS samples were analyzed for FDPs including PCA and UCA, as these FDPs reflect the level of FLG in the skin (33).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [33]
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- Authors
- Kezic, S., O’Regan, G. M., Yau, N., Sandilands, A., Chen, H., Campbell, L. E., Kroboth, K., Watson, R., Rowland, M., Irwin McLean, W. H., & Irvine, A. D.
- Affiliations
- Coronel Institute of Occupational Health, Academic Medical Center, Amsterdam, the Netherlands
- Children's Health Ireland at Crumlin (IE)
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Dundee (GB)
- Agency for Science, Technology and Research (SG)
- National Children’s Research Centre (IE)
- University College Dublin (IE)
- Division of Molecular Medicine, University of Dundee, Dundee, UK
- Trinity College Dublin (IE)
- Corresponding author
- Irvine, A. D.
- Venue
- Allergy
- Publisher
- Wiley
- Published
- 2011-01-25
- Volume
- 66
- Issue
- 7
- Pages
- 934-940
- ISSN
- 0105-4538 (ISSN-L)
- 1398-9995
- PMC
- PMC3586662
- OpenAlex
- W2159271088
- Cited by
- 295
- References
- 24
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 17 · 2023: 19 · 2022: 23 · 2021: 20 · 2020: 27 · 2019: 13 · 2018: 11 · 2017: 21 · 2016: 19 · 2015: 9 · 2014: 34 · 2013: 19 · 2012: 26
- FWCI
- 38.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Allergy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- filaggrin, FLG gene, atopic dermatitis, natural moisturizing factor, pyrrolidone carboxylic acid, urocanic acid, histidine, tyrosine, stratum corneum, disease severity, loss-of-function mutations, tape stripping, skin barrier
- MeSH terms
- Filaggrin Proteins, Child, Child, Preschool, Dermatitis, Atopic, Female, Genotype, Humans, Intermediate Filament Proteins, Male, Mutation, Pyrrolidonecarboxylic Acid, Severity of Illness Index, Skin, Urocanic Acid, Genetic Predisposition to Disease
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