Objective and design

Celiac disease (CD) is an intestinal inflammatory disorder of the small intestine. Gliadins are a component of gluten and there are three main types (α, γ, and ω). Recent studies indicate that gliadin peptides are able to activate an innate immune response. IL15 is a major mediator of the innate immune response and is involved in the early alteration of CD mucosa. The chitinase molecules are highly expressed by the innate immune cells during the inflammatory processes.

Material or subjects

We analyzed several microarray datasets of PBMCs and duodenum biopsies of CD patients and healthy control subjects (HCs). We verified the modulation CHI3L1 in CD patients and correlated the expression levels to the IL15, IL15Rα, TGM2, IFNγ, and IFNGR1/2. Duodenal biopsy samples belonged to nine active and nine treated children patients (long-term effects of gliadin), and 17 adult CD patients and 10 adults HCs. We also selected 169 samples of PBMCs from 127 CD patients on adherence to a gluten-free diet (GFD) for at least 2 years and 44 HCs.

Results

Our analysis showed that CHI3L1 and IL15Rα were significantly upregulated in adult and children’s celiac duodenum biopsies. In addition, the two genes were correlated significantly both in children than in adults CD duodenum biopsies. No significant modulation was observed in PBMCs of adult CD patients compared to the HCs. The correlation analysis of the expression levels of CHI3L1 and IL15Rα compared to TGM showed significant values both in adults and in children duodenal biopsies. Furthermore, the IFNγ expression levels were positively correlated with CHI3L1 and IL15Rα. Receiver operating characteristic (ROC) analysis confirmed the diagnostic ability of CHI3L1 and IL15Rα to discriminate CD from HCs.

Conclusion

Our data suggest a role for CHI3L1 underlying the pathophysiology of CD and represent a starting point aiming to inspire new investigation that proves the possible use of CHI3L1 as a diagnostic factor and therapeutic target.

中文翻译：

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CHI3L1 和 IL15Rα 的表达水平与乳糜泻患者十二指肠活检中的 TGM2 相关。

目标与设计

乳糜泻 (CD) 是一种小肠的肠道炎症性疾病。麦醇溶蛋白是面筋的一种成分，主要分为三种类型（α、γ 和 ω）。最近的研究表明，麦醇溶蛋白肽能够激活先天免疫反应。IL15 是先天免疫反应的主要介质，参与 CD 黏膜的早期改变。几丁质酶分子在炎症过程中由先天免疫细胞高度表达。

材料或主题

我们分析了 CD 患者和健康对照受试者 (HC) 的 PBMC 和十二指肠活检的几个微阵列数据集。我们验证了 CD 患者中 CHI3L1 的调节作用，并将表达水平与 IL15、IL15Rα、TGM2、IFNγ 和 IFNGR1/2 相关联。十二指肠活检样本属于 9 名活动患者和 9 名接受治疗的儿童患者（麦醇溶蛋白的长期影响），以及 17 名成人 CD 患者和 10 名成人 HC。我们还从 127 名坚持无麸质饮食 (GFD) 至少 2 年的 CD 患者和 44 名 HC 中选择了 169 份 PBMC 样本。

结果

我们的分析表明，CHI3L1 和 IL15Rα 在成人和儿童的腹腔十二指肠活检中显着上调。此外，这两个基因在儿童中比在成人 CD 十二指肠活检中显着相关。与 HC 相比，在成年 CD 患者的 PBMC 中未观察到显着的调节。CHI3L1 和 IL15Rα 表达水平与 TGM 相比的相关性分析在成人和儿童十二指肠活检中均显示出显着值。此外，IFNγ表达水平与CHI3L1和IL15Rα呈正相关。接受者操作特征 (ROC) 分析证实了 CHI3L1 和 IL15Rα 区分 CD 和 HC 的诊断能力。

结论

我们的数据表明 CHI3L1 在 CD 病理生理学中的作用，并代表了一个起点，旨在激发新的研究，证明 CHI3L1 可能用作诊断因子和治疗靶点。