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孕妇细胞因子谱可预测无哮喘母亲所生孩子的哮喘

Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma.

机构信息

1 Asthma and Airway Disease Research Center.

2 College of Nursing.

出版信息

Am J Respir Cell Mol Biol. 2018 Nov;59(5):592-600. doi: 10.1165/rcmb.2017-0410OC.

DOI:10.1165/rcmb.2017-0410OC
PMID:29863910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6236694/
Abstract

Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen-stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician-diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires. Maternal production of each of the cytokines IL-13, IL-4, IL-5, IFN-γ, IL-10, and IL-17 during pregnancy was unrelated to childhood asthma. However, IFN-γ/IL-13 and IFN-γ/IL-4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17-0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18-0.71; P = 0.003, respectively). The inverse relations of these two ratios with childhood asthma were only evident in mothers without asthma (n = 309; OR, 0.18; 95% CI, 0.08-0.42; P = 0.00007; and n = 299; OR, 0.17; 95% CI, 0.07-0.39; P = 0.00003, respectively) and not in mothers with asthma (n = 72 and 69, respectively; P for interaction by maternal asthma = 0.036 and 0.002, respectively). Paternal cytokine ratios were unrelated to childhood asthma. Maternal cytokine ratios in mothers without asthma were unrelated to the children's skin-test reactivity, total IgE, physician-confirmed allergic rhinitis at age 5, or eczema in infancy. To our knowledge, this study provides the first evidence that cytokine profiles in pregnant mothers without asthma relate to the risk for childhood asthma, but not allergy, and suggests a process of asthma development that begins in utero and is independent of allergy.

摘要

目前对于孕妇在怀孕期间的免疫状态是否会影响儿童的哮喘发病知之甚少。我们测量了来自图森婴儿免疫研究的儿童母亲在怀孕期间和之后外周血免疫细胞受刺激后上清液中细胞因子的产生情况,该研究为一个非选择性的出生队列。通过问卷调查评估了儿童在 9 岁前的医生诊断的活动性哮喘以及他们母亲的哮喘病史。母亲在怀孕期间产生的每种细胞因子(IL-13、IL-4、IL-5、IFN-γ、IL-10 和 IL-17)与儿童哮喘无关。然而,怀孕期间 IFN-γ/IL-13 和 IFN-γ/IL-4 的比值与儿童哮喘的风险降低相关(n = 381;比值比 [OR],0.33;95%置信区间 [CI],0.17-0.66;P = 0.002;n = 368;OR,0.36;95%CI,0.18-0.71;P = 0.003)。这两个比值与儿童哮喘之间的反比关系仅在没有哮喘的母亲中明显(n = 309;OR,0.18;95%CI,0.08-0.42;P = 0.00007;n = 299;OR,0.17;95%CI,0.07-0.39;P = 0.00003),而在有哮喘的母亲中不明显(n = 72 和 69,分别;母亲哮喘的交互作用 P 值为 0.036 和 0.002)。父亲的细胞因子比值与儿童哮喘无关。在没有哮喘的母亲中,母亲的细胞因子比值与儿童的皮肤试验反应性、总 IgE、5 岁时医生确诊的过敏性鼻炎或婴儿期特应性皮炎无关。据我们所知,这项研究首次提供了证据表明,没有哮喘的孕妇的细胞因子谱与儿童哮喘的风险有关,而与过敏无关,并表明哮喘的发展过程始于宫内,与过敏无关。

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Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.全表观基因组分析表明,哮喘母亲的孩子出生时SMAD3甲基化与儿童哮喘有关。
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