Affiliation:
1. Icahn School of Medicine at Mount Sinai Department of Dermatology and the Immunology Institute New York New York USA
2. Shaare Zedek Medical Center The Hebrew University of Jerusalem Jerusalem Israel
3. Laboratory for Investigative Dermatology The Rockefeller University New York New York USA
4. Department of Dermatology, Graduate School of Medical Sciences Kyushu University Fukuoka Japan
5. Department of Dermatology and Pediatrics Northwestern University Feinberg School of Medicine Chicago Illinois USA
Abstract
AbstractBackgroundWhile B‐cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B‐cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.ObjectiveTo compare the frequency of B‐cell subsets in blood of 0–5, 6–11, 12–17, and ≥18 years old patients with AD versus age‐matched controls.MethodsFlow cytometry was used to measure B‐cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate‐to‐severe AD and age‐matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11‐color flow cytometry panel were used to determine frequencies of circulating B‐cell subsets. Serum total and allergen‐specific IgE (sIgEs) levels were measured using ImmunoCAP®.ResultsAdolescents with AD had lower frequencies of major B‐cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL‐17‐producing T‐cells and B‐cell subsets, most significantly non‐switched memory (NSM) B‐cells (r = .41, p = .0005). AD severity positively correlated with a list of B‐cell subsets (p < .05). IL‐9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls.ConclusionsMultiple correlations between B‐cells and T‐cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B‐cell signature during adolescence, with concurrent allergen sensitization and IL‐9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.