Yue Molin, Gaietto Kristina, Han Yueh Ying, Rosser Franziska J, Xu Zhongli, Qoyawayma Christopher, Acosta-Perez Edna, Canino Glorisa, Forno Erick, Chen Wei, Celedón Juan C
Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA. 2025 Jan 28;333(4):307-318. doi: 10.1001/jama.2024.22684.
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.
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).
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.
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.
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.
辅助性T细胞2（T2）和辅助性T细胞17（T17）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对哮喘内型进行特征描述，对于开发针对哮喘青少年的有效疗法至关重要。
通过检查鼻上皮中转录组图谱的分布和特征，识别6至20岁学龄青少年的哮喘内型。
设计、背景和参与者：对来自3项针对6至20岁哮喘青少年研究的鼻上皮样本进行横断面分析：波多黎各和非裔美国哮喘儿童的压力与治疗反应（STAR；N = 156）、波多黎各人的表观遗传变异与儿童哮喘（EVA - PR；N = 237）以及维生素D与儿童哮喘（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图谱。在所有研究中，对各图谱的临床特征、总免疫球蛋白E（IgE）和过敏原特异性IgE、血液嗜酸性粒细胞以及肺功能进行了比较。
STAR、EVA - PR和VDKA参与者的平均年龄分别为14.2岁、15.4岁和10.3岁。各研究中女性参与者的比例在41%至53.2%之间。EVA - PR中主要种族或族裔是波多黎各人（100%），STAR中是黑人或非裔美国人（71.8%），VDKA中是黑人或非裔美国人（57.6%）。识别出三种转录组图谱：高T2表达（T2HIGH）、高T17表达（T17HIGH）以及两种通路低表达（T2LOW/T17LOW）。在各项研究中，T2HIGH出现在23%至29%的参与者中，T17HIGH出现在35%至47%的参与者中，T2LOW/T17LOW出现在30%至38%的参与者中。在每项研究中，T2HIGH图谱的总IgE中位数和血液嗜酸性粒细胞高于T2LOW图谱（IgE，584 - 869 vs 105 - 382 IU/mL；嗜酸性粒细胞，343 - 560 vs 164 - 413个细胞/mL）。在所有图谱的参与者中，至少50%有1种或更多种阳性过敏原特异性IgE。一项差异表达荟萃分析分别为T2HIGH和T17HIGH图谱鉴定出3516个和2494个差异表达基因。T17HIGH图谱与白细胞介素17和中性粒细胞信号通路相关，T2HIGH图谱与白细胞介素13信号通路相关。
在3项主要针对种族和族裔少数的哮喘青少年研究中，与T2高、T17高和T2低/T17低内型一致的鼻转录组图谱出现比例相似。大多数参与者具有T2低哮喘内型，并且在这些内型中对1种或更多种过敏原致敏很常见。
