touchDERMATOLOGY coverage of data presented at AAAAI/WAO 2025:
Atopic dermatitis (AD) is a chronic inflammatory skin condition affecting approximately 10–30% of children worldwide.¹ Early-onset AD often emerges by age two and may precede other allergic diseases like asthma and food allergies.² Beyond physical discomfort, it can significantly impact children and their families, contributing to sleep disturbances, emotional distress, financial burdens and social challenges.³ Early identification of AD could help carers anticipate symptoms, seek timely specialist care, and potentially help prevent other atopic diseases associated with early-onset AD.
Understanding that recent research has shown a link between DNA methylation (DNAm) and AD, investigators from Henry Ford Health sought to determine whether DNAm at birth could predict early-onset AD by analyzing cord-blood DNAm in individuals with and without early-onset AD by age two.4 Results from their study were presented at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in San Diego (February 28 – March 3).
To learn more about how the study was conducted, its findings, and the potential impact on clinical practice, we spoke with the lead investigator, Dr. Amy Eapen (Assistant Clinical Professor, Henry Ford Health System & Michigan State University, Detroit, MI, USA).
Q. What is the rationale for investigating the cord-blood methylome in early-onset AD?
Early-onset AD affects approximately 30% of children worldwide and is often the first sign of an allergic condition that may lead to other allergies, such as food allergies and asthma.
What we currently lack is a way to predict which children will develop AD early on, specifically by age two. Our rationale was that cord-blood is somewhat similar to a newborn screening test, as it can be investigated at birth. DNA methylation, in particular, is influenced by two key factors associated with atopic dermatitis: environmental factors and genetics.
Q. Could you summarize the methods used to characterize cord-blood DNAm in children with and without early-onset AD by age 2 years?
We utilized our population birth cohort at Henry Ford Health, called WHEALS, which recruited children in the early 2000s and collected cord blood at that time, and extracted the DNA from that. We then applied the custom content Asthma&Allergy array, developed by Carol Ober at the University of Chicago, designed as a booster to the Illumina EPIC array, to analyze DNA methylation in blood.
We then applied this approach to approximately 306 children from the WHEALS cohort, including those with and without early-onset AD by age two. AD was defined based on physician diagnoses made during clinic visits.
After that, we examined whether DNA methylation at individual CpG sites differed between children with early-onset AD and those without. We then analyzed regions of the genome to identify if there were clusters of methylation that occurred in those with AD versus those without AD. We then created a methylation risk score based on the differentially methylated sites to assess whether we could accurately predict at birth, if a child was likely to have AD.
Q. What were the key findings from the study?
Our key findings were that we could actually predict AD by age two with a very high sensitivity and specificity. We created a methylation risk score consisting of approximately 180 CpG sites that were differentially methylated in children with atopic dermatitis by age two, based on the cord-blood methylome. Our sensitivity was approximately 85%, and our specificity was around 86%. When we developed the methylation risk score, the area under the curve (AUC) was 0.94. Analyzing this, what we can say is that we found that DNA methylation at birth could be a good predictor of AD by age two.
Q. What is the potential clinical significance of these findings?
These findings are extremely clinically significant because they suggest a potential way to identify children with AD early at birth. Identifying AD early could provide appropriate anticipatory guidance not only for practitioners but also for families, helping them understand what to expect when they see a rash on their baby. This could also allow them to seek timely care from the appropriate providers, whether dermatologists, allergists, or immunologists, and potentially help prevent other atopic diseases associated with early-onset AD, such as food allergies.
Q. What questions remain unanswered, and what future studies do you think are needed to support your findings?
As exciting as these findings are, several questions remain unanswered. One key question is how the methylation sites we observed at specific parts of the genome affect gene expression. Is it affecting certain pathways?
From our findings, we observed enrichment for MHC class II antigen presentation, IFN-gamma signaling, and T-cell signaling pathways, which could serve as potential focal points for future clinical studies and therapeutic interventions for these children.
Another aspect we don’t yet understand is how the environment influences these methylation sites and subsequently leads to overt clinical disease. Future studies should investigate this in larger and diverse populations to better understand how environmental factors and genetics may contribute to these methylation sites.
References
- Tian J, Zhang D, Yang Y, Huang Y, Wang L, Yao X, Lu Q. Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study. Br J Dermatol. 2023 Dec 20;190(1):55-61.
- Pesonen M, Kallio MJT, Ranki A, Siimes MA, Järvinen KM. Early-onset atopic dermatitis and food hypersensitivity increase the risk of atopic march. Clin Exp Allergy. 2022 Sep;52(9):1110-1113. doi: 10.1111/cea.14189. Epub 2022 Jun 28.
- Yang EJ, Beck KM, Sekhon S, Bhutani T, Koo J. The impact of pediatric atopic dermatitis on families: A review. Pediatr Dermatol. 2019 Jan;36(1):66-71. doi: 10.1111/pde.13727. Epub 2018 Dec 16.
- Eapen A, Loveless I, Mingming et al. The impact of the cord blood methylome on early-onset atopic dermatitis. J Allergy Clin Immunol. 2025;155(Suppl.):Abstract L17
Associated abstract: Eapen A, Loveless I, Mingming et al. The impact of the cord blood methylome on early-onset atopic dermatitis. J Allergy Clin Immunol. 2025;155(Suppl.):Abstract L17
Click here for the full abstract.
Further content in dermatitis.
Disclosures: Dr Amy Eapen has nothing to disclose in relation to this interview.
This content has been developed independently by Touch Medical Media for touchDERMATOLOGY and is not affiliated with the AAAAI or the WAO. Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Interviewer/Editor: Gina Furnival
Cite: Specific cord-blood DNA methylation patterns associated with risk of early-onset atopic dermatitis. touchDERMATOLOGY, March 3 2025.
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