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A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease.
Digestive Diseases and Sciences ( IF 3.1 ) Pub Date : 2019-11-28 , DOI: 10.1007/s10620-019-05966-z
Karla A Bascuñán 1, 2 , Francisco Pérez-Bravo 1, 3 , Gabriella Gaudioso 4 , Valentina Vaira 4, 5 , Leda Roncoroni 2 , Luca Elli 2, 5 , Erika Monguzzi 2, 5 , Magdalena Araya 3, 6
Affiliation  

Background

The role of microRNAs (miRNAs) in celiac disease (CD) is unclear.

Aims

We evaluated inflammation-related miRNA-146a, miRNA-155, miRNA-21, and miRNA-125b expression in peripheral blood and intestinal mucosa of CD adults.

Methods

Thirty patients with CD were included: patients with active CD on a gluten-containing diet (CD-active, n = 10), patients on a gluten-free diet (for at least 1 year), and patients with negative blood antibodies (CD-inactivePE, n = 10). In addition, ten healthy volunteers formed the comparison/control group. MiRNA expression was measured in duodenal biopsies from patients (CD-inactiveMU, n = 10) after in vitro exposure to PT gliadin and 33-mer peptide. MiRNAs expression was measured in plasma and in peripheral blood mononuclear cells (PBMCs) and monocytes, before and after in vitro exposure to native gliadin (gliadinN).

Results

Expression levels of miRNA-146a, miRNA-155, and miRNA-21 in PBMCs, miRNA-155 in monocytes and miRNA-155, miRNA-21, and miRNA-125b in plasma were elevated in both groups of celiac patients. After in vitro exposure with gliadinN, miRNA-146a and miRNA-155 expression markedly increased in PBMCs and monocytes, while miRNA-155 and miRNA-21 increased in the CD-active group. MiRNAs expression in intestinal mucosa did not change. MiRNA-146a and miRNA-155 expression showed high sensitivity and specificity for the presence of CD, irrespective of the current dietary treatment.

Conclusions

Selected inflammation-related miRNAs expression is elevated in the peripheral blood of celiac. This suggests their participation in the immune processes underlying the pathology. Their similar response in active and inactive CD suggests that they should be further evaluated, as potential diagnostic biomarkers for CD.



中文翻译:

基于miRNA的血液和粘膜方法,用于检测和监测乳糜泻。

背景

microRNA(miRNA)在乳糜泻(CD)中的作用尚不清楚。

目的

我们评估了CD成人的外周血和肠粘膜中与炎症相关的miRNA-146a,miRNA-155,miRNA-21和miRNA-125b的表达。

方法

包括CD的30例患者:含麸质饮食中具有活动性CD的患者(CD活性,n  = 10),无麸质饮食中的患者(至少1年)和血液抗体阴性的患者(CD -无效的PEn  = 10)。另外,由十名健康志愿者组成比较/对照组。 在体外暴露于PT麦醇溶蛋白和33-mer肽后,在患者的十二指肠活检(CD无效的MUn = 10)中测量了miRNA的表达。在体外暴露于天然麦醇溶蛋白(麦醇溶蛋白N)之前和之后,在血浆,外周血单核细胞(PBMC)和单核细胞中测量MiRNA的表达。

结果

在两组乳糜泻患者中,PBMC中的miRNA-146a,miRNA-155和miRNA-21,单核细胞中的miRNA-155以及血浆中的miRNA-155,miRNA-21和miRNA-125b的表达水平均升高。在体外用麦醇溶蛋白N暴露后,PBMC和单核细胞中miRNA-146a和miRNA-155的表达明显增加,而CD活性组中miRNA-155和miRNA-21的表达增加。肠粘膜中的MiRNA表达没有变化。无论当前的饮食疗法如何,miRNA-146a和miRNA-155的表达均对CD的存在表现出高度的敏感性和特异性。

结论

选定的炎症相关miRNA表达在腹腔外周血中升高。这表明他们参与了病理基础的免疫过程。它们在有活性和无活性CD中的相似反应表明,应进一步评估它们,作为CD的潜在诊断生物标志物。

更新日期:2019-11-28
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