Allergy | Puberty-Stage B-Cell Subpopulations and Allergen Sensitization Specificity in Atopic Dermatitis

This study systematically analyzed the dynamic changes in B-cell subpopulations in atopic dermatitis (AD) patients from infancy to adulthood, revealing that adolescents with AD exhibit unique B-cell characteristics correlated with allergen sensitization and elevated IL-9 levels. These findings suggest puberty as a critical window for intervening in the atopic march.

 

Literature Overview
The article 'Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood' published in the journal Allergy reviews the age-dependent shifts in B-cell subpopulations among AD patients across different life stages and their associations with allergen-specific IgE (sIgE) and T-cell responses. Using flow cytometry, the study analyzed B-cell subsets in 27 infants, 17 children, 11 adolescents, and 31 adults with AD compared to healthy controls, while measuring total serum IgE and sIgE levels. The research further employed principal component analysis (PCA) and unsupervised clustering to identify distinct immunological features in adolescent AD patients, providing potential targets for modulating the atopic march.

Background Knowledge
Atopic dermatitis (AD) is a chronic inflammatory skin disease often initiating the atopic march, followed by food allergy, asthma, and allergic rhinitis. Previous studies focused on B-cell roles in allergic responses, but this work is the first systematic longitudinal analysis of B-cell differentiation trajectories from infancy to adulthood in AD patients, particularly their connections with allergen sensitization and T-cell cytokines like IL-17 and IL-9. The CD27/IgD and CD24/CD38 dual-marker systems employed are standard for flow cytometry-based B-cell maturation staging. CD23, a low-affinity IgE receptor, is upregulated in B-cell-mediated allergic reactions, while IL-9 is linked to allergic inflammation and mast cell proliferation. Despite partial studies on B cells in AD, systematic comparisons of B-cell subsets across age groups and their allergen-sensitization relationships were lacking. This study fills this gap and identifies adolescence as a potential intervention window for the atopic march.

 

 

Research Methods and Experiments
The research team conducted immunophenotyping of peripheral blood mononuclear cells (PBMCs) from AD patients and age-matched controls using flow cytometry with CD27/IgD and CD24/CD38 dual-marker systems to identify B-cell subsets. Total serum IgE and environment-specific sIgE levels were quantified via ImmunoCAP®. The study cohort included 27 infants (<5 years), 17 children (5–11 years), 11 adolescents (12–17 years), and 31 adults (≥18 years) with AD. Clinical severity (SCORAD, EASI, ADQ) and epidermal function (TEWL) were correlated with B-cell subsets and T-cell cytokine profiles.

Key Conclusions and Perspectives

• Adolescents with AD showed significant reductions in major B-cell subsets (e.g., non-switched memory B cells, switched memory B cells, double-negative memory B cells) but increased naive B-cell proportions, indicating abnormal B-cell differentiation during puberty.
• CD23+ B cells were elevated across all age groups of AD patients and correlated positively with disease severity, highlighting their central role in allergen presentation and IgE responses.
• In AD patients, IL-17A+ CD4+/CD8+ T cells showed positive correlations with B-cell subsets, particularly non-switched memory B cells (r=0.41, P=0.0005), suggesting Th17-B-cell interactions in AD immunoregulation.
• Principal component analysis (PCA) revealed unique sIgE clustering patterns in adolescent AD patients, indicating puberty as a peak period for allergen sensitization and a critical intervention window.
• AD severity correlated positively with multiple B-cell subsets, including IgE+ SM B cells, naive B cells, and total CD19+CD20+ B cells, demonstrating B-cell regulatory roles in disease phenotypes.

Research Significance and Prospects
This study provides the first comprehensive analysis of age-dependent B-cell subset evolution in AD patients, emphasizing adolescence as a key immunological remodeling phase. The findings suggest that targeting B cells and their regulators (e.g., CD23, IL-9) during puberty may effectively modulate AD progression and related allergic diseases. Future research should explore B-cell–T-cell interaction mechanisms and evaluate therapeutic strategies targeting B-cell or T-cell pathways in AD management.

 

 

Conclusion
This study systematically characterized B-cell subset evolution in AD patients from infancy to adulthood, identifying puberty as a critical immunological remodeling stage. Elevated CD23+ B cells, IL-9, and allergen sensitization peaks during adolescence suggest this phase as a key intervention window for the atopic march. Significant positive correlations between IL-17A+ T cells and B-cell subsets (particularly non-switched memory B cells) demonstrate B-cell–T-cell interactions in AD immunoregulation. These findings provide theoretical foundations for developing B-cell-targeted immunotherapies and emphasize the importance of longitudinal studies to validate the temporal sequence of immunological changes and their causal relationships in AD progression.

 

Tali Czarnowicki, Eden David, Kazuhiko Yamamura, Amy S Paller, and Emma Guttman-Yassky. Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood. Allergy.