| Autor: |
Richie Jeremian, PhD, Alexandra Malinowski, PhD, Edward S. Oh, PhD, Melinda Gooderham, MD, MSc, FRCPC, Cathryn Sibbald, MD, MSc, FRCPC, Jensen Yeung, MD, FRCPC, Yuka Asai, MD, FRCPC, Vincent Piguet, MD, PhD, FRCP, Carolyn S. Jack, MDCM, PhD, FRCPC |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Journal of Allergy and Clinical Immunology: Global, Vol 3, Iss 3, Pp 100275- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2772-8293 |
| DOI: |
10.1016/j.jacig.2024.100275 |
| Popis: |
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from the complex interplay of genetic and environmental factors, meriting exploration using temporally dynamic biomarkers. DNA methylation–based algorithms have been trained to accurately estimate biological age, and deviation of predicted age from true age (epigenetic age acceleration) has been implicated in several inflammatory diseases, including asthma. Objective: We sought to determine the role of epigenetic and biological aging, telomere length, and epigenetically inferred abundance of 7 inflammatory biomarkers in AD. Methods: We performed DNA methylation–based analyses in a pediatric AD cohort (n = 24, mean ± standard deviation [SD] age 2.56 ± 0.28 years) and age-matched healthy subjects (n = 24, age 2.09 [0.15] years) derived from blood using 5 validated algorithms that assess epigenetic age (Horvath, Skin&Blood) and biological age (PhenoAge, GrimAge), telomere length (TelomereLength), and inflammatory biomarker levels. Results: Epigenetic and biological age, but not telomere length, were accelerated in AD patients for 4 algorithms: Horvath (+0.88 years; 95% confidence interval [CI], 0.33 to 1.4; P = 2.3 × 10−3), Skin&Blood (+0.95 years; 95% CI, 0.67 to 1.2; P = 1.8 × 10−8), PhenoAge (+8.2 years; 95% CI, 3.4 to 13.0; P = 1.3 × 10−3), and GrimAge (+1.8 years 95% CI, 0.22 to 3.3; P = .026). Moreover, patients had increased levels of β2 microglobulin (+47,584.4 ng/mL; P = .029), plasminogen activation inhibitor 1 (+3,432.9 ng/mL; P = 1.1 × 10−5), and cystatin C (+31,691 ng/mL; P = 4.0 × 10−5), while levels of tissue inhibitor metalloproteinase 1 (−370.7 ng/mL; P = 7.5 × 10−4) were decreased compared to healthy subjects. Conclusion: DNA methylation changes associated with epigenetic and biological aging, and inflammatory proteins appear early in life in pediatric AD and may be relevant clinical biomarkers of pathophysiology. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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