Esophageal Mucosal Permeability as a Surrogate Measure of Cure in Eosinophilic Esophagitis.

Esophageal Mucosal Permeability as a Surrogate Measure of Cure in Eosinophilic Esophagitis.
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DOI:
10.3390/jcm11144246
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发表时间:
2022-07-21
影响因子:
3.9
通讯作者:
--
中科院分区:
医学2区
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--
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本研究旨在探讨嗜酸性食管炎(EoE)患者治疗前后上皮通透性与肥大细胞浸润、IgG4沉积及趋化因子水平的关系。对对照组和EoE患者治疗前后的活检标本进行分析。苏木精-伊红染色显示嗜酸性粒细胞浸润。用表面生物素标记法测定食道上皮细胞旁通透性。免疫组织化学染色检测肥大细胞浸润和IgG4沉积情况。采用定量逆转录-聚合酶链式反应检测趋化因子的基因表达。EoE患者食道上皮肥大细胞浸润、IgG4沉积和通透性明显增加。EoE患者白细胞介素13、钙蛋白酶14和嗜酸性粒细胞趋化蛋白3mRNAs水平显著上调,而丝氨酸蛋白、丝氨酸肽酶抑制剂Kazal 7型(SPINK7)和包皮蛋白mRNAs水平显著下调。在通过嗜酸性粒细胞计数诊断为组织学缓解的患者中,部分治疗后通透性不变的EoE患者显示肥大细胞浸润增加,IgG4沉积,白细胞介素13、钙蛋白酶-14、微丝蛋白和SPINK7表达增加,嗜酸性粒细胞趋化蛋白-3和总蛋白减少。其他通透性降低的EoE患者则表现为嗜酸性粒细胞趋化蛋白-3、包膜蛋白和肥大细胞浸润减少,无IgG4沉积,而IL-13、Calain-14、微丝蛋白和SPINK7升高。无嗜酸性粒细胞浸润的EoE患者治疗后食道通透性增加与肥大细胞浸润和IgG4沉积有关。
This study aimed to evaluate the relationship of esophageal epithelial permeability with mast cell infiltration and IgG4 deposits as well as chemokine levels in eosinophilic esophagitis (EoE) patients before and after treatment. Biopsies from controls and EoE patients before and after treatment were analyzed. Hematoxylin and eosin staining was used to show eosinophil infiltration. Paracellular permeability of the esophageal epithelium was assessed using surface biotinylation. Immunohistochemical staining was performed to examine mast cell infiltration and IgG4 deposits. Gene expression of chemokines was evaluated by qRT-PCR. Esophageal epithelial infiltration of mast cells, IgG4 deposits, and permeability were significantly increased in EoE patients. Levels of interleukin-13, calpain-14, and eotaxin-3 mRNAs were significantly upregulated, while filaggrin, serine peptidase inhibitor Kazal type 7 (SPINK7), and involucrin mRNAs were significantly downregulated in EoE patients. In patients achieving histologic remission diagnosed by eosinophil counts, a subset of EoE patients with unchanged permeability after treatment showed increases in mast cell infiltration, IgG4 deposits, and interleukin-13, calpain-14, filaggrin, and SPINK7 expression, with decreased eotaxin-3 and involucrin. Other EoE patients with decreased permeability displayed decreased eotaxin-3, involucrin, and mast cell infiltration, no IgG4 deposits, and increased IL-13, calpain-14, filaggrin, and SPINK7. Increased permeability of the esophagus in EoE patients without eosinophil infiltration after treatment was associated with mast cell infiltration and IgG4 deposits.
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