Early-life protein-bound skin ceramides help predict the development of atopic dermatitis

Chia-Lun Chang¹, Evgeny Berdyshev², Elasma Milanzi³, Caroline J Lodge³, Diego J Lopez³, Irina Bronova², Jennifer J Koplin⁴, Rachel L Peters⁵, Mimi L K Tang⁶, Shyamali C Dharmage¹, Michael J Abramson⁷, Jennie Hui⁸, George Varigos⁹, Kirsten P Perrett¹⁰, Arun Sasi¹¹, Jennifer L Perret³, John C Su¹², Paul D Robinson¹³, Donald Y M Leung¹⁴, Adrian J Lowe¹⁵

Affiliations

¹ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia.
² Department of Medicine, National Jewish Health, Denver, Colo.
³ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
⁴ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Child Health Research Centre, University of Queensland, South Brisbane, Australia.
⁵ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
⁶ Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy Immunology, Murdoch Children Research Institute, Parkville, Australia; Department of Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia.
⁷ School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Busselton Health Study Laboratory, Busselton Population Medical Research Institute, Busselton, Australia; Department of Diagnostic Genomics, PathWest Laboratory Medicine of West Australia, Nedlands, Australia; School of Population and Global Health, University of West Australia, Nedlands, Australia.
⁹ Dermatology, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
¹⁰ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Department of Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia.
¹¹ Mercy Hospital for Women, Heidelberg, Melbourne, Australia.
¹² Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Dermatology, Monash University, Eastern Health, Melbourne, Australia.
¹³ Children's Health and Environment Program, Child Health Research Centre, University of Queensland, Brisbane, Australia.
¹⁴ Department of Pediatrics, National Jewish Health, Denver, Colo.
¹⁵ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Allergy Immunology, Murdoch Children Research Institute, Parkville, Australia. Electronic address: lowea@unimelb.edu.au.

PMID: 39945702
DOI: 10.1016/j.jaci.2024.10.041

Free article

Early-life protein-bound skin ceramides help predict the development of atopic dermatitis

Chia-Lun Chang et al. J Allergy Clin Immunol. 2025 Mar.

Free article

. 2025 Mar;155(3):856-864.

doi: 10.1016/j.jaci.2024.10.041. Epub 2025 Feb 11.

Authors

Affiliations

¹ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia.
² Department of Medicine, National Jewish Health, Denver, Colo.
³ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
⁴ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Child Health Research Centre, University of Queensland, South Brisbane, Australia.
⁵ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
⁶ Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy Immunology, Murdoch Children Research Institute, Parkville, Australia; Department of Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia.
⁷ School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Busselton Health Study Laboratory, Busselton Population Medical Research Institute, Busselton, Australia; Department of Diagnostic Genomics, PathWest Laboratory Medicine of West Australia, Nedlands, Australia; School of Population and Global Health, University of West Australia, Nedlands, Australia.
⁹ Dermatology, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
¹⁰ Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Department of Allergy & Immunology, Royal Children's Hospital, Melbourne, Australia.
¹¹ Mercy Hospital for Women, Heidelberg, Melbourne, Australia.
¹² Population Allergy, Murdoch Children Research Institute, Parkville, Australia; Department of Dermatology, Monash University, Eastern Health, Melbourne, Australia.
¹³ Children's Health and Environment Program, Child Health Research Centre, University of Queensland, Brisbane, Australia.
¹⁴ Department of Pediatrics, National Jewish Health, Denver, Colo.
¹⁵ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Centre for Food Allergy Research, Murdoch Children's Research Institute, Parkville, Australia; Allergy Immunology, Murdoch Children Research Institute, Parkville, Australia. Electronic address: lowea@unimelb.edu.au.

PMID: 39945702
DOI: 10.1016/j.jaci.2024.10.041

Abstract

Background: Skin lipids are crucial components of the skin barrier. Individuals with atopic dermatitis (AD or eczema) have a different skin lipid profile from those without. However, whether altered skin lipids precede and predict the subsequent risk of AD remained unclear, especially for different AD phenotypes.

Objective: We sought to examine the relationship between skin lipids and subsequent AD and AD phenotypes in infants.

Methods: Skin lipids from the forearms of 133 infants with family history of allergic disease were sampled using tape strips at age 6 weeks. Lipids were quantified using liquid chromatography-tandem mass spectrometry. AD by age 1 year was diagnosed using modified UK Working Party Criteria. Allergic sensitization was assessed using skin prick tests. Associations and predictive discrimination were estimated using univariable logistic regression. Potential causation was explored using multivariable logistic regression.

Results: Reduced levels of 6 protein-bound ω-hydroxyl sphingosine (POS) ceramides with C30 and C32 fatty acids at 6 weeks were associated with increased risk of AD by age 1 year. In univariate models, a number of POS ceramides predicted subsequent AD, such as PO30:0-C20S (area under the curve, 0.65; 95% CI, 0.55-0.75). After confounders were adjusted, only PO30:0-C20S was associated with AD (adjusted odds ratio, 0.62; 95% CI, 0.39-0.96 per 1-SD increase), and a trend for AD without sensitization (adjusted odds ratio, 0.57; 95% CI, 0.31-1.05) but not AD with sensitization (adjusted odds ratio, 0.76; 95% CI, 0.39-1.47).

Conclusions: Reduced levels of POS ceramides are associated with the development of nonatopic AD, suggesting that these lipids may play a role in the pathogenesis of AD and may be useful predictive biomarkers. Interventions that increase POS ceramides may reduce the incidence of AD.

Keywords: Atopic dermatitis; ceramides; eczema; protein-bound ceramides; skin barrier.

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Conflict of interest statement

Disclosure statement PEBBLES is funded by the National Health and Medical Research Council of Australia (NHMRC, grant nos. 1130010, 2013620, and 2015248). C.C. is supported by the University of Melbourne, Centre for Food Allergy Research, and the Taiwanese Government Scholarship to Study Abroad for undertaking this research. C.J.L., J.L.P., and S.C.D. are funded by the NHMRC Investigator Grants. Funds from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (grant no. 5UM1AI130780) partially supported analyses of skin tapes. Disclosure of potential conflict of interest: A. J. Lowe, C. J. Lodge, S. C. Dharmage, J. L. Perret, and M. J. Abramson have received an investigator-initiated grant from GlaxoSmithKline (GSK) for unrelated research, and S. C. Dharmage and J. L. Perret also hold a similar grant from AstraZeneca. A. J. Lowe has received an investigational product (EpiCeram) free of charge from Primus Pharmaceuticals for use in unrelated research. A. J. Lowe, S. C. Dharmage, and J. J. Koplin have received grant funding from Sanofi Regeneron for unrelated research. M. J. Abramson holds grants from Pfizer, Boehringer-Ingelheim, Sanofi, and GSK for unrelated research and has also undertaken an unrelated consultancy for Sanofi and received a speaker’s fee from GSK. D. Y. M. Leung has received grant funding from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (grant nos. 5UM1AI130780, 1UM1AI151958, and 1R01AI147462) and The Edelstein Family Chair of Pediatric Allergy-Immunology to study the development of eczema in infants and young children. E. Berdyshev and D. Y. M. Leung received research contracts from Sanofi and LEO Pharma to study eczema in children. K. P. Perrett has received research grants from Aravax, DBV Technologies, Novartis, and Siolta Therapeutics and consultant fees from Aravax paid to their institution, outside the submitted work. J. C. Su has received grants from Abbvie, Amgen, ASLAN, BMS, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pierre Fabre, Pfizer, and Sanofi for unrelated research paid to his institutions. R. L. Peters has received a prize from the Stallergenes Greer Foundation paid to their institution outside the submitted work and received speaker fees from Stallergenes Greer, outside the submitted work. J. J. Koplin received a research award from the Stallergenes Greer Foundation, paid to her institution, unrelated to the current manuscript. M. L. K. Tang declares consultant fees from CSL Seqirus and Pfizer; inventorship on patents covering Peanut Oral Immunotherapy; consultant to and holding share interest and options in Prota Therapeutics; member of the Medical Advisory Board of Anaphylaxis & Anaphylaxis Australia; member of the Board of Directors of Asia Pacific Association of Allergy Asthma and Clinical Immunology, Prota Therapeutics and AllergyPAL; member of expert committees of the American Academy of Allergy, Asthma & Immunology, Asia Pacific Association of Allergy Asthma and Clinical Immunology, and Australasian Society of Clinical Immunology and Allergy. The rest of the authors declare that they have no relevant conflicts of interest.

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Early-life protein-bound skin ceramides help predict the development of atopic dermatitis

Affiliations

Early-life protein-bound skin ceramides help predict the development of atopic dermatitis

Authors

Affiliations

Abstract

Conflict of interest statement

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