Sebum transcriptome data predict development of atopic dermatitis in young infants
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Key takeaways:
- Infants with atopic dermatitis at age 1 month had higher expression of genes involved in immune responses.
- Sebum collection represents a noninvasive technique for predicting atopic dermatitis in young infants.
Molecular changes in barrier function and inflammatory markers characterized the pathophysiology of atopic dermatitis at age 1 month, according to a study published in the Journal of the European Academy of Dermatology and Venereology.
Using sebum transcriptome data, neonatal acne at age 1 month could be used to predict subsequent development of AD as well, Kiwako Yamamoto-Hanada, MD, PhD, chief of the Allergy Center, National Center for Child Health and Development (NCCHD), and colleagues wrote.
“Infants often have multiple eczemas and experience repeated exacerbations and remissions,” Yamamoto-Hanada said in a press release. “With our method, the timely treatment of early onset AD can be realized, enabling an improvement in the quality of life for infants with AD and their families.”
The prospective cohort study involved 98 infants (52 boys) born at the NCCHD between July and November 2020. These infants visited the NCCHD at age 1, 2 and 6 months, where certified allergists evaluated their skin at each visit. Also, researchers collected skin surface lipids (SSLs) and purified SSL-RNAs.
The cohort included 46 (46.9%) with a family history of atopic dermatitis and 88 (89.8%) with a family history of allergy. Also, 11 (11.2%) were diagnosed with AD at age 1 month, and 40 (40.8%) were diagnosed with neonatal acne at age 1 month.
Using differential expression analysis, the researchers found 461 upregulated genes and 793 downregulated genes among the infants with AD at age 1 month as well as 98 upregulated genes and 580 downregulated genes at age 2 months.
Gene ontology (GO) analysis with a database for annotation, visualization and integrated discovery (DAVID) found that keratinization, the lipid metabolic process and the sphingolipid biosynthetic process were significantly enriched among infants with AD, the researchers said.
The downregulated genes in the infants with AD at age 1 month included those related to various lipid syntheses and metabolisms. Lipid-related genes included those related to ceramide synthesis and metabolism, fatty acid synthesis and metabolism, wax ester and triglyceride synthesis, and cholesterol metabolism.
The expression of genes related to serine proteases and antimicrobial activity were downregulated in infants with AD as well. Additionally, testing revealed genes related to tight junction, desmosome formation, natural moisturizing factor synthesis and epidermal cornification.
Infants with AD also had significantly enriched immune response, type 1 interferon signaling pathway, innate immune response and defense response to virus in their upregulated genes.
Further, the researchers said they confirmed that the expression of genes related to various T cells was related to inflammation. Genes associated with Th2-type, Th17-type, Th22-type, and Th17/22-type immune response had significantly higher expression in infants with AD at age 1 month.
Infants with AD had significantly lower expression of IL-37 and PTGER3, which are negative regulators of inflammation, the researchers said, but genes related to innate immunity and Th1-type immune response had significantly higher expression.
Additionally, innate immune response-related genes had higher expression and pathogen recognition-related TLR2 and TLR4 had significantly higher expression in infants with AD than in healthy infants, the researchers said.
Differential expression analysis also found 59 upregulated genes and 420 downregulated genes among infants with neonatal acne age 1 month and AD at age 2 months compared with infants with neonatal acne at age 1 month but no AD at age 2 months.
The oxidation reduction and cholesterol biosynthetic processes as well as phosphatidylserine acyl-chain remodeling were significantly enriched in these 420 downregulated genes, the researchers said.
Based on gene set variation analysis (GSVA), infants with neonatal acne at age 1 month and AD at age 2 months had significantly lower enrichment scores compared with infants with neonatal acne at age 1 month and no AD at age 2 months and with healthy infants, although their scores were favorable compared with those of infants with AD at age 1 month.
Infants with neonatal acne had 248 upregulated genes enriched with immune response compared with healthy infants. Infants with AD had 176 downregulated genes enriched with barrier-related GO terms including keratinization, sphingolipid biosynthetic process and ceramide compared with those infants with neonatal acne.
Further GSVA of barrier-related genes found significantly lower enrichment scores among infants with neonatal acne at age 1 month and AD at age 2 months compared with infants with neonatal acne at age 1 month and no AD at age 2 months and with healthy infants, the researchers said.
Using logistic regression analysis, the researchers found that the GSVA score derived from the SSL-RNA expression levels of infants with neonatal acne at age 1 month could determine whether they would develop AD at age 2 months.
There was a correlation between the GO-included GSVA score and the barrier-related GSVA score (Spearman’s rho = 0.912; P < .001), the researchers said, but combining these scores did not improve their accuracy.
Univariate logistic regression analysis also found 50 genes including epidermal lipid metabolism-related molecules that were statistically significant variables in discriminating between infants with AD and those who did not have AD at age 2 months.
Finally, the researchers found that GO-included and barrier-related GSVA scores and the expression levels of some genes in these gene lists obtained by SSL-RNA analysis in infants with neonatal acne at age 1 month may predict AD onset up to age 2 months.
By using sebum transcriptome data and SSL-RNA analysis, the researchers said, physicians can noninvasively evaluate molecular changes that reflect the pathogenesis of AD in young infants who have fragile skin without the use of skin biopsies or tape stripping.
“Our results confirm that the RNA monitoring method is useful for the early detection of AD in infants and may also be used for their treatment monitoring in the future,” Yamamoto-Hanada said in the release.
The researchers next plan on further studies that will diagnose AD among various populations and monitor AD status during treatment.
Reference:
- A novel way to diagnose early-onset atopic dermatitis using sebum. https://www.kao.com/global/en/newsroom/news/release/2023/20230608-001/. Published June 8, 2023. Accessed June 20, 2023.
Perspective
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The results of this study are interesting, with the authors using a noninvasive technique in SSL-RNA to identify immune and barrier abnormalities in infants with AD. These results are in line with previous studies using a different noninvasive technique to collect RNA with tape strips. Additionally, the authors found an association with neonatal acne that could predict subsequent development of AD, which may help to inform clinical care by increasing attention and evaluation of infants with neonatal acne for AD in the ensuing months. Next steps in this research may be directed toward applying these techniques to further understand and characterize which infants may be at risk for developing AD, as well as to improve the understanding of what time points sampling techniques might be most leveraged in the future to help predict the development of AD.
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