TY - JOUR
T1 - Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood
AU - Czarnowicki, Tali
AU - David, Eden
AU - Yamamura, Kazuhiko
AU - Han, Joseph
AU - He, Helen
AU - Pavel, Ana B.
AU - Glickman, Jacob
AU - Erickson, Taylor
AU - Estrada, Yeriel
AU - Krueger, James G.
AU - Rangel, Stephanie M.
AU - Paller, Amy S.
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2024/10
Y1 - 2024/10
N2 - Background: While 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. Objective: To 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. Methods: Flow 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®. Results: Adolescents 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. Conclusions: Multiple 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.
AB - Background: While 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. Objective: To 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. Methods: Flow 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®. Results: Adolescents 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. Conclusions: Multiple 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.
KW - allergy
KW - atopic dermatitis
KW - B-cells
KW - CD23
KW - IgE
KW - IL-9
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U2 - 10.1111/all.16225
DO - 10.1111/all.16225
M3 - Article
C2 - 39003573
AN - SCOPUS:85198536935
SN - 0105-4538
VL - 79
SP - 2732
EP - 2747
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 10
ER -