Proteomic characterization of atopic dermatitis blood from infancy to adulthood

Background: Atopic dermatitis/AD patients have systemic biomarker dysregulation that differs by age group, but proteomic characteristics of these age-based changes are unknown. Objective: To profile blood proteins of AD patients across different age groups versus age-appropriate controls. Methods: Using the OLINK high-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (0-5y/o), 39 children (6-11y/o), 21 adolescents (12-17y/o), and 20 adults (≥18y/o) with moderate-to-severe AD, and 83 age-appropriate controls. Results: Each group presented a distinct systemic proteomic signature. Th2-related proteins were increased in infant AD and further intensified with age through adolescence and adulthood (IL-4/CCL13/CCL17). In contrast, Th1 axis down-regulation was detected in infants with AD and gradually reversed to increased Th1 products (IFN/CXCL9/CXCL10/CCL2) in AD patients from childhood to adulthood. Despite their short disease duration, infants already have evidence of systemic inflammation, with significant up-regulation of general inflammatory (MMP12), innate (IL-17C/IL-1RN), T-cell activation/migration (CD40LG/CCL19), Th2 (IL-10/CCL13/CCL17), and Th17 (PI3) proteins (p<0.05). AD Adults present unique up-regulation of cardiovascular proteins related with coagulation and diabetes. Limitations: Cross-sectional observational study with a single time-point. Conclusions: Systemic immune signatures of AD are age-specific beyond the shared Th2 immune activation. These data advocate for precision medicine approaches based on age-specific AD profiles.背景：特应性皮炎（Atopic Dermatitis，AD）患者存在系统性生物标志物失调，且该失调特征存在年龄差异，但此类年龄相关变化的蛋白质组学特征目前尚不明确。 研究目的：对比不同年龄组特应性皮炎患者与同年龄段健康对照的血液蛋白质组表达谱。 研究方法：本研究采用OLINK高通量蛋白质组学平台，对100名中重度特应性皮炎患者（含20名0~5岁婴儿、39名6~11岁儿童、21名12~17岁青少年、20名≥18岁成人）及83名同年龄段健康对照者的375种血清蛋白质进行了表达谱分析。 研究结果：各患者组均呈现出独特的系统性蛋白质组特征。辅助性T细胞2（Th2）相关蛋白在婴儿期特应性皮炎患者中即出现升高，并随年龄增长在青少年及成人患者中进一步增强（IL-4/CCL13/CCL17）。与之相反，特应性皮炎婴儿患者中检测到辅助性T细胞1（Th1）轴下调，而从儿童期至成人期的特应性皮炎患者中，Th1相关效应分子（IFNγ/CXCL9/CXCL10/CCL2）的表达逐渐恢复至上调状态。尽管病程较短，婴儿特应性皮炎患者已出现系统性炎症证据：其一般性炎症相关（MMP12）、天然免疫相关（IL-17C/IL-1RN）、T细胞活化/迁移相关（CD40LG/CCL19）、Th2相关（IL-10/CCL13/CCL17）及Th17相关（PI3）蛋白均出现显著上调（p<0.05）。成人特应性皮炎患者则呈现出与凝血及糖尿病相关的心血管蛋白的独特上调。 研究局限性：本研究为单时间点横断面观察性研究。 研究结论：特应性皮炎的系统性免疫特征具有年龄特异性，且超出了共通的Th2免疫激活范畴。本研究数据支持基于年龄特异性特应性皮炎特征的精准医学策略。