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Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients
Open accessAbstract
A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. We demonstrate for the first time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.
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“In cases of AD, there is a decreased amount of ceramides and those present are shorter.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [55]
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“The lipid matrix of the stratum corneum is defective in AD skin due to an alteration in the expression of enzymes involved in the synthesis and processing of free fatty acids and ceramides.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [55]
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“The composition of ceramide classes/species in the human SC has previously been analyzed using LC/MS (5-7, 16, 17, 29, 30).”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [17]
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Metadata
- Authors
- Janssens, M., van Smeden, J., Gooris, G. S., Bras, W., Portale, G., Caspers, P. J., Vreeken, R. J., Hankemeier, T., Kezic, S., Wolterbeek, R., Lavrijsen, A. P., & Bouwstra, J. A.
- Affiliations
- Leiden University (NL)
- Dutch Research Council (NL)
- Erasmus MC (NL)
- Leiden University Medical Center (NL)
- Corresponding author
- Bouwstra, Joke A.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 53
- Issue
- 12
- Pages
- 2755-2766
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3494247
- OpenAlex
- W2130942098
- Cited by
- 488
- References
- 75
- Citations by year
- 2026: 31 · 2025: 37 · 2024: 47 · 2023: 30 · 2022: 36 · 2021: 42 · 2020: 39 · 2019: 41 · 2018: 37 · 2017: 32 · 2016: 32 · 2015: 28 · 2014: 33 · 2013: 20
- FWCI
- 32.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- H2020 European Research Council
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- atopic dermatitis, short-chain ceramides, skin barrier dysfunction, stratum corneum lipids, lipid organization, filaggrin, non-lesional skin, disease severity
- MeSH terms
- Filaggrin Proteins, Adult, Ceramides, Dermatitis, Atopic, Female, Genotype, Humans, Intermediate Filament Proteins, Male, Mutation, Molecular Structure, Lipid Metabolism
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