Epithelioid granulomas, pattern recognition receptors, and phenotypes of Crohn's disease
Epithelioid granulomas, pattern recognition receptors, and phenotypes of Crohn's disease
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DOI：
10.1136/gut.2004.042572
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发表时间：
2005-02-01
期刊：
影响因子：
24.5
通讯作者：
Geboes, K
中科院分区：
文献类型：
--
作者：
Pierik, M;De Hertogh, G;Geboes, K
简介：克罗恩病是一种肠道慢性炎症性疾病。据认为，肠道菌群与先天免疫系统之间的相互作用缺陷在该疾病的发病机制中发挥着关键作用。这可能导致特定的组织学病变。上皮样肉芽肿在这方面特别有趣，因为它也在肠道的几种细菌感染中观察到。 目的和方法：我们假设已知对炎症或免疫有影响的遗传或环境因素会导致肉芽肿患病率增加。因此，对 161 名患者的手术标本进行了肉芽肿的存在评估。对患者进行了与 CD 相关的 caspase 募集结构域 15 (CARD15)/NOD2 中的三个单核苷酸多态性以及 Toll 样受体 4 (TLR4) 中的 Asp299Gly 的基因分型。结果：肉芽肿的总体患病率为 68.9%。我们没有发现肉芽肿与 TLR4 或 CARD15 变异之间存在显着相关性。肉芽肿的发生率随着远端疾病的增加而增加（63% 小肠、72% 右结肠、88% 左结肠、90% 直肠；p = 0.01）。肉芽肿在年轻患者中更为常见（比值比 0.95（95% 置信区间 0.92 - 0.98）p = 0.007）。结论：在这项针对 161 名有据可查的 CD 患者的研究中，我们发现 CARD15 和 TLR4 变异与肉芽肿之间没有显着关联。这一发现似乎反驳了我们最初的假设。然而，肉芽肿的形成可能还需要其他因素。仅当存在特定细菌成分时才可能出现肉芽肿。因此，未来肉芽肿发病机制的研究应面向这些病变中细菌成分的检测和鉴定。
Introduction: Crohn's disease is a chronic inflammatory disorder of the gut. It is assumed that a defective interaction between the bacterial flora of the gut and the innate immune system plays a key role in the pathogenesis of the disease. This may lead to specific histological lesions. The epithelioid granuloma is particularly interesting in this regard as it is also observed in several bacterial infections of the gut.Aims and methods: We hypothesised that genetic or environmental factors with a known influence on inflammation or immunity would lead to an increased prevalence of granulomas. Therefore, surgical specimens from 161 patients were evaluated for the presence of granulomas. Patients were genotyped for the three single nucleotide polymorphisms in caspase recruitment domain 15 ( CARD15)/NOD2 associated with CD and for Asp299Gly in Toll-like receptor 4 (TLR4).Results: The overall prevalence of granulomas was 68.9%. We did not find a significant correlation between granulomas and TLR4 or CARD15 variants. The frequency of granulomas increased with more distal disease (63% small bowel, 72% right colon, 88% left colon, 90% rectum; p = 0.01). Granulomas were more frequent in younger patients ( odds ratio 0.95 (95% confidence interval 0.92 - 0.98) p = 0.007).Conclusion: In this study of 161 well documented CD patients, we found no significant association between CARD15 and TLR4 variants and granulomas. This finding seems to refute our initial hypothesis. However, it may be that additional factors are needed for granuloma development. Granulomas may develop only when specific bacterial components are present. Therefore, future research on granuloma pathogenesis should be orientated towards detection and identification of bacterial components in these lesions.