Icahn School of Medicine at Mount Sinai, Department of Dermatology and the Immunology Institute, New York, New York, USA.
Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Allergy. 2024 Oct;79(10):2732-2747. doi: 10.1111/all.16225. Epub 2024 Jul 14.
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.
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.
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®.
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.
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.
虽然 B 细胞一直以来都被认为与过敏反应的发展有关，但越来越多的证据支持它们在特应性皮炎（AD）中的作用。AD 患者不同年龄段的 B 细胞分化及其与疾病严重程度评分的关系尚未得到很好的定义。
比较 AD 患者和年龄匹配的对照组中 0-5 岁、6-11 岁、12-17 岁和≥18 岁患者血液中 B 细胞亚群的频率。
采用流式细胞术检测 27 例婴儿、17 例儿童、11 例青少年和 31 例中重度 AD 患者及年龄匹配的对照组血液中 B 细胞亚群的频率。使用 IgD/CD27 和 CD24/CD38 核心门控系统和 11 色流式细胞术面板确定循环 B 细胞亚群的频率。使用 ImmunoCAP®测定血清总 IgE（sIgE）和过敏原特异性 IgE（sIgE）水平。
AD 青少年的主要 B 细胞亚群频率较低（p<0.03）。CD23 的表达随年龄增长而增加，且在所有年龄组中 AD 患者的表达均高于对照组（p<0.04）。在 AD 患者中，IL-17 产生的 T 细胞与 B 细胞亚群之间存在多种正相关，尤其是非转换记忆（NSM）B 细胞（r=0.41，p=0.0005）。AD 严重程度与一系列 B 细胞亚群呈正相关（p<0.05）。IL-9 水平在儿童期逐渐升高，在青春期达到峰值，与变应原致敏平行，尤其是在重度 AD 中。对聚集的环境 sIgE 数据进行主成分分析显示，尽管所有年龄段的对照组紧密聚集在一起，但 AD 青少年相对于对照组表现出独特的聚类模式。
B 细胞与 T 细胞之间以及与疾病严重程度指标之间的多种相关性表明 AD 中存在复杂的免疫途径相互作用。青春期特有的 B 细胞特征，同时伴有变应原致敏和 IL-9 激增，表明有机会实施可能预防特应性进行曲进展的干预措施。
