美国匹兹堡大学Juan C. Celedón团队进行了青少年鼻上皮和哮喘内型的转录组学分析。2025年1月2日出版的《美国医学会杂志》发表了这项成果。

T辅助2（T2）细胞和T辅助17（T17）细胞是参与哮喘的CD4+T细胞亚型。在不同群体中基于这些细胞类型来表征哮喘内型对于开发针对哮喘青少年的有效疗法非常重要。

为了通过检测鼻上皮细胞转录组谱的分布和特征，鉴定6~20岁学龄青年的哮喘内型，研究组对3项6至20岁哮喘青少年研究的鼻上皮样本进行了横断面分析：波多黎各和非裔美国哮喘儿童的压力和治疗反应（STAR；N = 156），波多黎各人的表观遗传变异和儿童哮喘（EVA-PR；N=237），维生素D儿童哮喘（VDKA；N=66）。主要结局是3个T2和5个T17通路基因的鼻上皮转录谱。在所有研究中，对临床特征、总免疫球蛋白E（IgE）和过敏原特异性IgE、血液嗜酸性粒细胞和肺功能进行了比较。

STAR、EVA-PR和VDKA参与者的平均年龄分别为14.2、15.4和10.3岁。在所有研究中，女性参与者的比例从41%到53.2%不等。EVA-PR中的主要种族或民族是波多黎各人（100%），STAR（71.8%）和VDKA（57.6%）中主要为黑人或非裔美国人。共鉴定了三种转录组谱：高T2表达（T2HIGH）、高T17表达（T17HIGH）和两种途径的低表达（T2LOW/T17LOW）。在所有研究中，23%至29%的参与者存在T2HIGH，35%至47%存在T17HIGH，30%至38%存在T2LOW/T17LOW。

在每项研究中，T2HIGH谱的总IgE和血液嗜酸性粒细胞中位数高于T2LOW谱（IgE，584-869 vs 105-382 IU/mL；嗜酸性粒血球，343-560 vs 164-413细胞/mL）。在所有资料的参与者中，至少50%的人有1个或多个过敏原特异性IgE阳性。差异表达荟萃分析分别鉴定了3516和2494个T2HIGH和T17HIGH谱的差异表达基因。T17HIGH谱与白细胞介素17和中性粒细胞信号通路有关，T2HIGH谱与白细胞介素13信号通路有关。

在这3项主要针对美国少数种族和族裔哮喘青少年的研究中，与T2高、T17高和T2低/T17低内型一致的鼻转录组特征的比例相似。大多数参与者具有T2低哮喘内型，对1种或多种过敏原的敏感性在这些内型中很常见。

附：英文原文

Title: Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth

Author: Molin Yue, Kristina Gaietto, Yueh Ying Han, Franziska J. Rosser, Zhongli Xu, Christopher Qoyawayma, Edna Acosta-Perez, Glorisa Canino, Erick Forno, Wei Chen, Juan C. Celedón

Issue&Volume: 2025-01-02

Abstract:

Importance  T helper 2 (T2) cells and T helper 17 (T17) cells are CD4+ T cell subtypes involved in asthma. Characterizing asthma endotypes based on these cell types in diverse groups is important for developing effective therapies for youths with asthma.

Objective  To identify asthma endotypes in school-aged youths aged 6 to 20 years by examining the distribution and characteristics of transcriptomic profiles in nasal epithelium.

Design, Setting, and Participants  Cross-sectional analysis of nasal epithelial samples from 3 studies of youths with asthma aged 6 to 20 years: Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR; N=156), Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR; N=237), and Vitamin D Kids Asthma (VDKA; N=66).

Main Outcomes and Measures  The primary outcome was nasal epithelial transcription profiles of 3 T2 and 5 T17 pathway genes. Clinical characteristics, total and allergen-specific immunoglobulin E (IgE), blood eosinophils, and lung function were compared across profiles in all studies.

Results  Mean ages for STAR, EVA-PR, and VDKA participants were 14.2, 15.4, and 10.3 years, respectively. The percentage of female participants ranged from 41% to 53.2% across studies. The predominant race or ethnicity was Puerto Rican in EVA-PR (100%) and Black or African American in STAR (71.8%) and VDKA (57.6%). Three transcriptomic profiles were identified: high T2 expression (T2HIGH), high T17 expression (T17HIGH), and low expression of both pathways (T2LOW/T17LOW). Across studies, T2HIGH was present in 23% to 29% of participants, T17HIGH in 35% to 47%, and T2LOW/T17LOW in 30% to 38%. In each study, median total IgE and blood eosinophils for the T2HIGH profile was higher than for the T2LOW profiles (IgE, 584-869 vs 105-382 IU/mL; eosinophils, 343-560 vs 164-413 cells/mL). Of the participants in all profiles, at least 50% had 1 or more positive allergen-specific IgEs. A differential expression meta-analysis identified 3516 and 2494 differentially expressed genes for the T2HIGH and T17HIGH profiles, respectively. The T17HIGH profile was associated with interleukin 17 and neutrophil signaling pathways and the T2HIGH profile was associated with interleukin 13 signaling pathways.

Conclusions and Relevance  Nasal transcriptomic profiles consistent with T2-high, T17-high, and T2-low/T17-low endotypes occurred in similar proportions across 3 studies of predominantly racially and ethnically minoritized youths with asthma. Most participants had T2-low asthma endotypes and sensitization to 1 or more allergens was common among these endotypes.

DOI: 10.1001/jama.2024.22684

Source: https://jamanetwork.com/journals/jama/fullarticle/2828721