成人特应性中的分子致敏聚类：一项基于ALEX2的东欧分析

文献信息

中文摘要

背景： 过敏原致敏谱存在地域差异，但东欧数据仍然匮乏。本研究旨在使用ALEX2多重检测，在罗马尼亚一家三级过敏中心识别并描述患有过敏性鼻炎（AR）、哮喘和/或特应性皮炎（AD）的成人中的分子致敏聚类。
方法： 在213名连续接受ALEX2检测的成人（2024年1月至2026年5月）中，161名确诊AR、哮喘或AD者构成研究人群。其中，139名至少有一种可检测过敏原致敏者被纳入基于98种过敏原的Ward.D2层次聚类分析。关联性采用Fisher精确检验并以Benjamini-Hochberg校正进行评估。
结果： 本研究在罗马尼亚成人特应性队列中识别出四个主要分子过敏原致敏聚类，并通过探索性的五聚类细化进一步解析了优势聚类内部的异质性。聚类1（少致敏，n=42）尽管致敏广度最低（中位数2种致敏）且总IgE最低（133.5 kU/L），却矛盾地显示出较高的哮喘患病率（54.8%），但该发现在全局聚类比较中未达到显著性，应视为探索性。聚类2（禾本科花粉优势，n=24）和聚类3（多致敏，n=47）显示几乎普遍存在AR。聚类4（多泛过敏原PR-10/nsLTP，n=10）口腔过敏综合征（OAS）发生率最高（30%），由PR-10和nsLTP驱动；而聚类5（豚草和抑制蛋白优势，n=16）显示完全由抑制蛋白介导的OAS。年龄与致敏广度呈负相关（Spearman r= -0.265，p=0.0016），老年患者总IgE反而升高。
结论： 对ALEX2数据的无监督聚类在罗马尼亚成人特应性队列中识别出四种主要分子致敏表型，并通过探索性五分类细化解析出额外的临床相关异质性，是东欧首批此类特征描述之一。关键临床见解包括一个伴探索性哮喘富集的少致敏聚类以及一个区域特异性的豚草/抑制蛋白聚类，凸显了多重分子谱分析在成人特应性疾病中的实用性。

英文摘要

BACKGROUND: Allergen sensitization profiles vary geographically, yet Eastern Europe data remain scarce. This study aimed to identify and characterize molecular sensitization clusters in adults with allergic rhinitis (AR), asthma, and/or atopic dermatitis (AD) at a Romanian tertiary allergy center using ALEX2 multiplex profiling.
METHODS: Among 213 consecutive adults undergoing ALEX2 testing (January 2024-May 2026), 161 with confirmed AR, asthma, or AD formed the study population. Of these, 139 with at least one detectable allergen sensitization were included in Ward.D2 hierarchical clustering across 98 allergens. Associations were evaluated using Fisher's exact test with Benjamini-Hochberg correction.
RESULTS: The present study identified four primary molecular allergen sensitization clusters in an adult atopic cohort from Romania, with an exploratory, five-cluster refinement further resolving heterogeneity within the dominant cluster. Cluster 1 (pauci-sensitized, n=42) paradoxically showed a high asthma prevalence (54.8%) despite the lowest sensitization breadth (median 2 sensitizations) and total IgE (133.5 kU/L), though this finding did not reach significance in the global cluster comparison and should be considered exploratory. Cluster 2 (grass pollen-dominant, n=24) and Cluster 3 (polysensitized, n=47) showed near-universal AR prevalence. Cluster 4 (multi-panallergen PR-10/nsLTP, n=10) carried the highest rate of oral allergy syndrome (OAS) (30%), driven by PR-10 and nsLTP, whereas Cluster 5 (ragweed and profilin-dominant, n=16) showed exclusively profilin-mediated OAS. Age was negatively correlated with sensitization breadth (Spearman r= -0.265, p=0.0016), with paradoxically elevated total IgE in older patients.
CONCLUSION: Unsupervised clustering of ALEX2 data identified four primary molecular sensitization phenotypes in a Romanian adult atopic cohort, with an exploratory five-way refinement resolving additional clinically relevant heterogeneity, representing one of the first such characterizations from Eastern Europe. Key clinical insights include a pauci-sensitized cluster with an exploratory enrichment for asthma and a region-specific ragweed/profilin cluster, highlighting the utility of multiplex molecular profiling in adult atopic disease.