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乳糜泻患者十二指肠中人β防御素 1 的低表达部分可通过无麸质饮食得到恢复。

Low expression of human beta-defensin 1 in duodenum of celiac patients is partially restored by a gluten-free diet.

机构信息

Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy.

出版信息

Clin Chem Lab Med. 2010 Apr;48(4):489-92. doi: 10.1515/CCLM.2010.098.

DOI:10.1515/CCLM.2010.098
PMID:20128731
Abstract

BACKGROUND

Human beta-defensins (hBDs) are small cationic, widely expressed proteins involved in innate immunity that exert strong bactericidal activity toward various pathogens. However, the role of hBDs in various diseases to which bacterial infection add severity, as it is in celiac disease (CD), is not yet clear. We analyzed the expression of the hBD1, hBD2, hBD3 and hBD4 genes in patients with CD during the active phase and after remission following a gluten-free diet to determine their role in development and relapse of CD.

METHODS

We studied 21 unrelated adults with CD (confirmed by anti-thyroglobulin antibodies and intestinal biopsy); 14 were evaluated at diagnosis, before diet modification, and seven after 2 years of a gluten-free diet. Thirty-six unrelated adults served as controls. We analyzed the mRNA expression of hBD1, 2, 3 and 4 on biopsy samples of duodenum obtained from all patients during endoscopy for diagnostic purposes. We used real-time polymerase chain reaction with TaqMan probes and obtained gene expression data using the delta-Ct method.

RESULTS

hBD1 mRNA was significantly lower in patients with active CD compared with patients on diet modification, whereas the mRNA levels of the other three defensins did not differ significantly between the two subgroups. Interestingly, the gluten-free diet restored only partially hBD1 expression as compared to a normal group of celiac-free subjects.

CONCLUSIONS

Our data reinforce the evidence that hBD1 expression is greatly reduced in the duodenum of patients with active CD. It also strengthens the concept that reduced activity of immune peptides may predispose individuals to bacterial proliferation that contributes to the pathogenesis of CD.

摘要

背景

人β-防御素(hBDs)是一种小的阳离子、广泛表达的蛋白,参与固有免疫,对各种病原体具有强烈的杀菌活性。然而,hBDs 在各种疾病中的作用尚不清楚,这些疾病中细菌感染会加重病情,如在乳糜泻(CD)中。我们分析了处于活动期的 CD 患者和无麸质饮食缓解后的 CD 患者的 hBD1、hBD2、hBD3 和 hBD4 基因表达,以确定它们在 CD 的发展和复发中的作用。

方法

我们研究了 21 名无关的成人 CD 患者(通过抗甲状腺球蛋白抗体和肠活检证实);14 名在诊断时、改变饮食前进行评估,7 名在无麸质饮食 2 年后进行评估。36 名无关的成年人作为对照组。我们分析了所有患者内镜诊断时十二指肠活检样本中 hBD1、2、3 和 4 的 mRNA 表达。我们使用 TaqMan 探针的实时聚合酶链反应,并使用 delta-Ct 方法获得基因表达数据。

结果

与饮食改变的患者相比,处于活动期 CD 的患者 hBD1 mRNA 显著降低,而其他三种防御素的 mRNA 水平在这两个亚组之间没有显著差异。有趣的是,与无麸质饮食组相比,无麸质饮食仅部分恢复了 hBD1 的表达。

结论

我们的数据加强了证据表明,hBD1 在活动期 CD 患者的十二指肠中表达大大降低。它还强化了这样的概念,即免疫肽活性降低可能使个体易发生细菌增殖,从而导致 CD 的发病机制。

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