Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Gut. 2010 Jan;59(1):12-20. doi: 10.1136/gut.2009.178020.
Eosinophilic oesophagitis (EO) is an emerging yet increasingly prevalent disorder characterised by a dense and selective eosinophilic infiltration of the oesophageal wall. While EO is considered an atopic disease primarily triggered by food antigens, disparities between standard allergen testing and clinical responses to exclusion diets suggest the participation of distinct antigen-specific immunoglobulin E (IgE) in the pathophysiology of EO.
To find evidence for a local IgE response.
Endoscopic biopsies of the distal oesophagus of atopic and non-atopic EO and control individuals (CTL) were processed for immunohistochemistry and immunofluorescence to assess the presence of B cells, mast cells, and IgE-bearing cells. Oesophageal RNA was analysed for the expression of genes involved in B cell activation, class switch recombination to IgE and IgE production, including germline transcripts (GLTs), activation-induced cytidine deaminase (AID), IgE heavy chain (Cepsilon) and mature IgE mRNA using polymerase chain reaction and microarray analysis.
Regardless of atopy, EO showed increased density of B cells (p<0.05) and of IgE-bounded mast cells compared to CTL. Both EO and CTL expressed muGLT, epsilonGLT, gamma4GLT, AID, Cepsilon and IgE mRNA. However, the frequency of expression of total GLTs (p = 0.002), epsilonGLT (p = 0.024), and Cepsilon (p = 0.0003) was significantly higher in EO than in CTL, independent of the atopic status.
These results support the heretofore unproven occurrence of both local immunoglobulin class switching to IgE and IgE production in the oesophageal mucosa of EO patients. Sensitisation and activation of mast cells involving local IgE may therefore critically contribute to disease pathogenesis.
嗜酸性粒细胞性食管炎 (EO) 是一种新兴的、越来越普遍的疾病，其特征是食管壁有密集且选择性的嗜酸性粒细胞浸润。虽然 EO 被认为是一种主要由食物抗原触发的特应性疾病，但标准过敏原测试与排除饮食后的临床反应之间的差异表明，在 EO 的病理生理学中存在不同的抗原特异性免疫球蛋白 E (IgE)。
寻找局部 IgE 反应的证据。
对特应性和非特应性 EO 以及对照个体 (CTL) 的远端食管进行内镜活检，进行免疫组织化学和免疫荧光分析，以评估 B 细胞、肥大细胞和携带 IgE 的细胞的存在。使用聚合酶链反应和微阵列分析分析食管 RNA 中参与 B 细胞激活、IgE 类别转换和 IgE 产生的基因的表达，包括种系转录物 (GLTs)、激活诱导的胞苷脱氨酶 (AID)、IgE 重链 (Cepsilon) 和成熟 IgE mRNA。
无论是否特应性，EO 与 CTL 相比，B 细胞密度增加 (p<0.05)，并且 IgE 结合的肥大细胞增加。EO 和 CTL 均表达 muGLT、epsilonGLT、gamma4GLT、AID、Cepsilon 和 IgE mRNA。然而，总 GLTs (p = 0.002)、epsilonGLT (p = 0.024) 和 Cepsilon (p = 0.0003) 的表达频率在 EO 中明显高于 CTL，与特应性状态无关。
这些结果支持迄今为止未经证实的 EO 患者食管黏膜中局部免疫球蛋白类转换为 IgE 和 IgE 产生的发生。涉及局部 IgE 的肥大细胞致敏和激活可能因此对疾病的发病机制至关重要。
