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儿童乳糜泻患者十二指肠远近端黏膜中 Claudin 2、3 和 4 的表达。

Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease.

机构信息

1st Department of Pediatrics, Semmelweis University, Bókay str. 53-54, 1083, Budapest, Hungary.

出版信息

Virchows Arch. 2010 Mar;456(3):245-50. doi: 10.1007/s00428-009-0879-7. Epub 2010 Feb 9.

Abstract

Duodenal biopsy is an important tool to diagnose coeliac disease (CD); however, the most reliable location of biopsy site is still questionable. Claudins (CLDNs), members of a large family of adherent junction proteins, show characteristic expression pattern in inflammatory disorders; nevertheless, CLDN expression in CD is unknown. This is a comparative study to examine the CLDN 2, 3 and 4 expressions in proximal and distal part of duodenum in children with CD and in controls. Thirty-three children with newly diagnosed CD were enrolled. Fourteen healthy children served as controls. Biopsies from proximal and distal part of duodenum were taken for routine histological analysis. Immunohistochemistry were used to detect CD3+ intraepithelial lymphocytes and CLDN 2, 3 and 4 protein expressions. Macroscopic picture, routine histology and Marsh grade depicted no differences between biopsies taken from proximal or distal part of duodenum. However, CLDN 2 expression was significantly increased in severe form of coeliac disease in bulb and in distal duodenum, and in distal part of non-severe coeliac patients, in comparison to controls. Similar association was found concerning CLDN 3 expression. Expression of CLDN 4 was similar in all groups studied. Both proximal and distal mucosal duodenal biopsies are suitable for diagnosing villous atrophy in patients with CD. Increased expressions of CLDN 2 and 3 suggest structural changes of tight junction in coeliac disease which may be, at least in part, responsible for increased permeability and proliferation observed in coeliac disease.

摘要

十二指肠活检是诊断乳糜泻 (CD) 的重要工具;然而,最可靠的活检部位仍存在疑问。紧密连接蛋白 (CLDNs) 是一大类黏附连接蛋白家族的成员,在炎症性疾病中表现出特征性的表达模式;然而,CD 中的 CLDN 表达情况尚不清楚。本研究旨在比较分析 CD 患儿和对照组近端和远端十二指肠中 CLDN2、3 和 4 的表达。纳入 33 例新诊断为 CD 的儿童。14 名健康儿童作为对照组。采集近端和远端十二指肠活检标本进行常规组织学分析。免疫组织化学用于检测 CD3+上皮内淋巴细胞和 CLDN2、3 和 4 蛋白表达。大体形态、常规组织学和 Marsh 分级显示近端和远端十二指肠活检之间无差异。然而,与对照组相比,球部和远端 CD 严重型以及非严重型 CD 患者的远端,CLDN2 表达显著增加。CLDN3 表达也存在类似的关联。CLDN4 的表达在所有研究组中相似。近端和远端黏膜十二指肠活检均适用于诊断 CD 患者的绒毛萎缩。CLDN2 和 3 的表达增加表明 CD 中紧密连接的结构发生变化,这至少部分解释了 CD 中观察到的通透性增加和增殖。

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