摘要
背景： 生命早期表观遗传编程可能介导复发性喘息和哮喘的基因－环境相互作用。多CpG甲基化评分可以总结超出观察到的免疫球蛋白E（IgE）水平所能反映的高IgE表观遗传潜力。
目的：建立并检验表观遗传－总IgE（DNAm-IgE）评分对儿科呼吸道疾病的残留影响。
方法：我们使用来自第35届多中心气道研究合作（MARC-35; n=560）、第43届多中心气道研究合作（MARC-43; n=177）和波士顿出生队列（BBC; n=80）的数据。DNA甲基化（Illumina EPIC阵列）在婴儿时期的血液（MARC-35, MARC-43）和出生时的脐带血（BBC）中进行测量。对所有队列的婴儿、3岁时反复喘息和6岁时哮喘患者的血液中总IgE进行评估。
结果：MARC-35数据用于训练和评估DNAm-IgE评分（R=0.502 vs.总IgE）。采用MARC-43和BBC数据验证评分（R=0.309和R=0.132）。在三个队列的荟萃分析中，1-SD的DNAm-IgE评分残差（DNAm-IgE评分与总IgE回归）与复发性喘息相关（OR=1.33[1.11,1.60]，异质性=0.92），而1-SD的总IgE与哮喘相关（OR=1.45[1.19,1.76]，异质性=0.29；所有模型均根据性别、种族/民族和出生体重进行调整）。
结论：生命早期与总免疫球蛋白E（IgE）相关的表观遗传模式可能会导致超出所测IgE水平的后续呼吸道疾病。DNA甲基化-IgE评分及其残差成分应被视为需要进一步验证和机制研究的探索性工具。
Infancy IgE Methylation Score and Childhood Wheezing and Asthma; a Multi-Cohort Study
Anat Yaskolka Meir, Yijun Li, Zhaozhong Zhu, Janice A Espinola, Xiumei Hong, Carlos A Camargo Jr, Xiaobin Wang, Kohei Hasegawa, Liming Liang
Abstract
Background: Early life epigenetic programming may mediate gene-environment interactions underlying recurrent wheezing and asthma. Multi-CpG methylation scores can summarize the epigenetic potential for high immunoglobulin E (IgE) beyond what is captured by observed IgE levels.
Objective: To establish and examine the residual effect of an epigenetic-total IgE (DNAm-IgE) score on respiratory morbidity in a pediatric population.
Methods: We used data from the 35th Multicenter Airway Research Collaboration (MARC-35; n=560), 43rd Multicenter Airway Research Collaboration (MARC-43; n=177), and the Boston Birth Cohort (BBC; n=80). DNA methylation (Illumina EPIC array) was measured in blood during infancy (MARC-35, MARC-43) and in cord blood at birth (BBC). Total IgE was assessed in blood at infancy, recurrent wheezing at age 3 years, and asthma at age 6 years for all cohorts.
Results: MARC-35 data were used to train and evaluate a DNAm-IgE score (R=0.502 vs. total IgE). MARC-43 and BBC data were used to validate the score (R=0.309 and R=0.132). In meta-analyses of the three cohorts, 1-SD of DNAm-IgE score residuals (DNAm-IgE score regressed on total IgE) was associated with recurrent wheezing (OR=1.33 [1.11,1.60], Pheterogeneity=0.92), while 1-SD total IgE was associated with asthma (OR=1.45 [1.19,1.76], Pheterogeneity=0.29; All models adjusted for sex, race/ethnicity, and birth weight).
Conclusion: Early-life epigenetic patterns related to total IgE may contribute to subsequent respiratory morbidity beyond measured IgE levels. The DNAm-IgE score and its residual component should be viewed as exploratory tools that require further validation and mechanistic study.
背景： 生命早期表观遗传编程可能介导复发性喘息和哮喘的基因－环境相互作用。多CpG甲基化评分可以总结超出观察到的免疫球蛋白E（IgE）水平所能反映的高IgE表观遗传潜力。
目的：建立并检验表观遗传－总IgE（DNAm-IgE）评分对儿科呼吸道疾病的残留影响。
方法：我们使用来自第35届多中心气道研究合作（MARC-35; n=560）、第43届多中心气道研究合作（MARC-43; n=177）和波士顿出生队列（BBC; n=80）的数据。DNA甲基化（Illumina EPIC阵列）在婴儿时期的血液（MARC-35, MARC-43）和出生时的脐带血（BBC）中进行测量。对所有队列的婴儿、3岁时反复喘息和6岁时哮喘患者的血液中总IgE进行评估。
结果：MARC-35数据用于训练和评估DNAm-IgE评分（R=0.502 vs.总IgE）。采用MARC-43和BBC数据验证评分（R=0.309和R=0.132）。在三个队列的荟萃分析中，1-SD的DNAm-IgE评分残差（DNAm-IgE评分与总IgE回归）与复发性喘息相关（OR=1.33[1.11,1.60]，异质性=0.92），而1-SD的总IgE与哮喘相关（OR=1.45[1.19,1.76]，异质性=0.29；所有模型均根据性别、种族/民族和出生体重进行调整）。
结论：生命早期与总免疫球蛋白E（IgE）相关的表观遗传模式可能会导致超出所测IgE水平的后续呼吸道疾病。DNA甲基化-IgE评分及其残差成分应被视为需要进一步验证和机制研究的探索性工具。
（北京朝阳医院呼吸与危重症医学科 顾宪民 摘译 中日友好医院呼吸与危重症医学科 林江涛 审校）
（J Allergy Clin Immunol. 2026 Mar 11:S0091-6749(26)00185-5. doi: 10.1016/j.jaci.2026.03.002. Online ahead of print.）
Infancy IgE Methylation Score and Childhood Wheezing and Asthma; a Multi-Cohort Study
Anat Yaskolka Meir, Yijun Li, Zhaozhong Zhu, Janice A Espinola, Xiumei Hong, Carlos A Camargo Jr, Xiaobin Wang, Kohei Hasegawa, Liming Liang
Abstract
Background: Early life epigenetic programming may mediate gene-environment interactions underlying recurrent wheezing and asthma. Multi-CpG methylation scores can summarize the epigenetic potential for high immunoglobulin E (IgE) beyond what is captured by observed IgE levels.
Objective: To establish and examine the residual effect of an epigenetic-total IgE (DNAm-IgE) score on respiratory morbidity in a pediatric population.
Methods: We used data from the 35th Multicenter Airway Research Collaboration (MARC-35; n=560), 43rd Multicenter Airway Research Collaboration (MARC-43; n=177), and the Boston Birth Cohort (BBC; n=80). DNA methylation (Illumina EPIC array) was measured in blood during infancy (MARC-35, MARC-43) and in cord blood at birth (BBC). Total IgE was assessed in blood at infancy, recurrent wheezing at age 3 years, and asthma at age 6 years for all cohorts.
Results: MARC-35 data were used to train and evaluate a DNAm-IgE score (R=0.502 vs. total IgE). MARC-43 and BBC data were used to validate the score (R=0.309 and R=0.132). In meta-analyses of the three cohorts, 1-SD of DNAm-IgE score residuals (DNAm-IgE score regressed on total IgE) was associated with recurrent wheezing (OR=1.33 [1.11,1.60], Pheterogeneity=0.92), while 1-SD total IgE was associated with asthma (OR=1.45 [1.19,1.76], Pheterogeneity=0.29; All models adjusted for sex, race/ethnicity, and birth weight).
Conclusion: Early-life epigenetic patterns related to total IgE may contribute to subsequent respiratory morbidity beyond measured IgE levels. The DNAm-IgE score and its residual component should be viewed as exploratory tools that require further validation and mechanistic study.
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