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Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis

机译：食管IgG4水平与嗜酸性食管炎中的组织病理学和转录组特征相关

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摘要

Abstract Background Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. Methods This case‐control study included pediatric subjects with EoE (≥15?eosinophils/HPF) and non‐EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1‐IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. Results Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2?mg/g protein [interquartile range: 1.0‐13.1?mg/g protein] vs 0.2?mg/g protein [0.1‐0.9]; P? ? .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts ( P? = ? .0006); histologic grade ( P? = ? .0011) and stage ( P? = ? .0112) scores; and IL4 , IL10 , IL13 , but not TGFB1 , expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. Conclusion These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally.
机译：摘要背景近期数据与IgG4而不是IgE的嗜酸性食管炎（EOE）源，但尚未确定其意义和功能。我们的目标是测量食管IgG4水平，并确定通过组织学和转录组分析评估的功能相关性。方法本病例对照研究包括具有eoe（≥15°粒细胞/ HPF）和非EOE控制的儿科对象。使用Luminex 100系统对IgA，IgM和IgG1-IgG4分析蛋白质裂解物; IgE通过ELISA量化。使用EOE组织学评分系统评分食管活组织检查。通过EoE诊断面板探测转录物，旨在检查96种食管转录物的表达。结果食道IgG亚类，IgA和IgM，但不是IgE，在具有相对于对照的eoE的受试者中增加。在IgG4（4.2×mg / g蛋白[四分位数范围：1.0-13.1×mg / g蛋白]中，群体之间的最大变化是0.2×mg / g蛋白[0.1-0.9];p≤≤00.0001） 。组织IgG4水平与食道嗜酸性粒细胞计数相关（P？=Δ0006）;组织学等级（p？=Δ0011）和阶段（p？=Δ0112）得分;和IL4，IL10，IL13，但不是TGFB1，表达并具有与EOE转录组的子集的强关节。食管IgG4转录物表达增加并与IgG4蛋白水平和IL10表达相关。结论这些研究结果在成人EOE中的IgG4对儿科人群进行了先前研究，并对IgG4的潜在意义和调节提供了更深的了解，表明IgG4是疾病的相关特征;与食管嗜酸性粒细胞水平密切相关，2型免疫和T调节细胞因子;并且很可能在本地生产。

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  • 来源
    《Allergy》 |2018年第9期|共10页
  • 作者

    Rosenberg C. E.; Mingler M. K.; Caldwell J. M.; Collins M. H.; Fulkerson P. C.; Morris D. W.; Mukkada V. A.; Putnam P. E.; Shoda T.; Wen T.; Rothenberg M. E.;

  • 作者单位

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Pathology and Laboratory MedicineUniversity of Cincinnati College of MedicineCincinnati;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Gastroenterology Hepatology and NutritionUniversity of Cincinnati College of;

    Division of Gastroenterology Hepatology and NutritionUniversity of Cincinnati College of;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

    Division of Allergy and ImmunologyUniversity of Cincinnati College of MedicineCincinnati OH USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    eosinophilic esophagitis; eosinophilic oesophagitis; histology; IgG4; pediatric; transcriptome;

    机译：嗜酸性食管炎;嗜酸性噬菌体嗜嗜酸性咽喉炎;组织学;IgG4;小儿;转录组;

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