Abstract：
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.
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.
摘要：
背景：虽然历史上B细胞与变态反应的发展有关，越来越多的证据支持它们在特应性皮炎（AD）中的作用。不同年龄的B细胞分化在AD中，以及它与疾病严重程度评分的关系，还没有很好的定义。
目的：比较0-5岁、6-11岁、12-17岁和≥18岁AD患者与年龄匹配对照者的血液中B细胞亚群的频率。
方法：流式细胞术用于测量27名婴儿血液中的B细胞亚群频率，17个孩子,11名青少年,和31名患有中度至重度AD和年龄匹配对照的成年人。使用IgD/CD27和CD24/CD38核心门控系统和11色流式细胞术小组来确定循环B细胞亚群的频率。使用ImmunoCAP®测量血清总和变应原特异性IgE(sIgEs)水平。
结果：患有AD的青少年主要B细胞亚群的频率较低（p<.03）。CD23表达随年龄增长而增加,并且在所有年龄组中与对照相比在AD中更高(p<.04)。在AD患者中，在产生IL-17的T细胞和B细胞亚群之间观察到多个正相关，最显著的非交换记忆(NSM)B细胞(r=.41，p=.0005)。AD严重程度与一系列B细胞亚群呈正相关(p<.05)。IL-9水平在儿童期逐渐升高，在青春期达到顶峰，平行过敏原致敏，尤其是严重的AD。汇总的环境sIgE数据的主成分分析显示，尽管所有年龄段的对照紧密地聚集在一起，与对照组相比，青少年AD表现出不同的聚类模式。
结论：B细胞和T细胞之间的多重相关性，以及疾病严重程度的措施，提示AD中免疫途径的复杂相互作用。青春期独特的B细胞特征，同时发生过敏原致敏和IL-9激增，指出实施干预措施可能会阻止特应性行军进展的潜在更广泛的机会窗口。
目的：比较0-5岁、6-11岁、12-17岁和≥18岁AD患者与年龄匹配对照者的血液中B细胞亚群的频率。
方法：流式细胞术用于测量27名婴儿血液中的B细胞亚群频率，17个孩子,11名青少年,和31名患有中度至重度AD和年龄匹配对照的成年人。使用IgD/CD27和CD24/CD38核心门控系统和11色流式细胞术小组来确定循环B细胞亚群的频率。使用ImmunoCAP®测量血清总和变应原特异性IgE(sIgEs)水平。
结果：患有AD的青少年主要B细胞亚群的频率较低（p<.03）。CD23表达随年龄增长而增加,并且在所有年龄组中与对照相比在AD中更高(p<.04)。在AD患者中，在产生IL-17的T细胞和B细胞亚群之间观察到多个正相关，最显著的非交换记忆(NSM)B细胞(r=.41，p=.0005)。AD严重程度与一系列B细胞亚群呈正相关(p<.05)。IL-9水平在儿童期逐渐升高，在青春期达到顶峰，平行过敏原致敏，尤其是严重的AD。汇总的环境sIgE数据的主成分分析显示，尽管所有年龄段的对照紧密地聚集在一起，与对照组相比，青少年AD表现出不同的聚类模式。
结论：B细胞和T细胞之间的多重相关性，以及疾病严重程度的措施，提示AD中免疫途径的复杂相互作用。青春期独特的B细胞特征，同时发生过敏原致敏和IL-9激增，指出实施干预措施可能会阻止特应性行军进展的潜在更广泛的机会窗口。
