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

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.