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首页> 外文期刊>Allergy >Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit
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Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit

机译：血液和鼻外膜血管生物学与环境暴露单位的过敏性鼻炎症状发展相关联

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摘要

Abstract Background Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis ( AR ). Our aim was to examine genome‐wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit ( EEU ). Methods 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells ( PBMC s) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini‐Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR . To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 ( MUC 4 ), in nasal brushings from a separate validation cohort exposed to birch pollen. Results In PBMC s of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 ( TPSG 1 ), schlafen 12 ( SLFN 12 ), and MUC 4 in response to exposure were validated by pyrosequencing. SLFN 12 DNA methylation significantly correlated with symptoms ( P 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure ( P = 0.029). Changes in MUC 4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC 4 gene expression was significantly increased ( P 0.0001). Conclusion This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.
机译：摘要背景表观遗传改变可能代表过敏性鼻炎（AR）的新治疗靶标和/或生物标志物。我们的目的是研究环境暴露单位（EEU）中受控花粉暴露诱导的全基因组脑膜遗传变化。方法38 AR患者和八种非极剂对照在连续两天将草花粉暴露3小时。我们使用Infinium甲基化450K阵列询问基线的DNA甲基化和3小时的外周血单核细胞（PBMC S）。我们纠正了人口统计学，细胞组成和多次测试（Benjamini-Hochberg），并使用Bisulfite PCR焦肌肉测序和QPCR进行了验证的命中。为了将这些发现延伸到临床相关的组织，我们研究了从暴露于桦树花粉的单独验证队列中的鼻蛋白4（MUC 4）的DNA甲基化和基因表达。结果在过敏性鼻炎参与者的PBMC S中，42个位点显示出显着的DNA甲基化变化2％或更高。通过焦肌肉进行验证，通过焦肌肉验证蛋白胨γ1（TPSG 1），SchlafeN 12（SLFN 12）和MUC4的DNA甲基化变化。 SLFN 12 DNA甲基化与症状显着相关（P <0.05），并发现基线DNA甲基化模式是在草过敏原暴露时预测症状严重程度（P = 0.029）。验证队列中的鼻胶凝中的MUC 4 DNA甲基化的变化与峰值鼻吸气流动（Spearman的R = 0.314，P = 0.034）相关，并且MUC4基因表达明显增加（P <0.0001）。结论本研究揭示了在受控过敏原挑战机构中暴露的新型和快速的表观遗传变化，并确定了基线表观遗传状态作为症状严重程度的预测因子。

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  • 来源
    《Allergy》 |2018年第1期|共10页
  • 作者

    North M. L.; Jones M. J.; MacIsaac J. L.; Morin A. M.; Steacy L. M.; Gregor A.; Kobor M. S.; Ellis A. K.;

  • 作者单位

    Department of Biomedical &

    Molecular Sciences and Division of Allergy &

    ImmunologyQueen's;

    BC Children's Hospital Research Institute and Centre for Molecular Medicine &

    BC Children's Hospital Research Institute and Centre for Molecular Medicine &

    BC Children's Hospital Research Institute and Centre for Molecular Medicine &

    Allergy Research UnitKingston General HospitalKingston ON Canada;

    Department of Biomedical &

    Molecular Sciences and Division of Allergy &

    ImmunologyQueen's;

    BC Children's Hospital Research Institute and Centre for Molecular Medicine &

    Department of Biomedical &

    Molecular Sciences and Division of Allergy &

    ImmunologyQueen's;

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  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    allergen challenge; allergic rhinitis; environmental exposure unit; epigenetics; pollen;

    机译：过敏原挑战;过敏性鼻炎;环境暴露单位;表观学报;花粉;

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