Department of Translational Medical Science, University of Naples Federico II, Naples, Italy ; European Laboratory for Food-Induced disease (ELFID), University of Naples Federico II, Naples, Italy ; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
PLoS One. 2013 Sep 17;8(9):e74747. doi: 10.1371/journal.pone.0074747. eCollection 2013.
Celiac disease (CD) is a multifactorial autoimmune disease induced by ingestion of gluten in genetically predisposed individuals. Despite technological progress, the diagnosis of CD is still based on duodenal biopsy as it was 50 years ago. In this study we analysed the expression of CD-associated genes in small bowel biopsies of patients and controls in order to explore the multivariate pathway of the expression profile of CD patients. Then, using multivariant discriminant analysis, we evaluated whether the expression profiles of these genes in peripheral blood monocytes (PBMs) differed between patients and controls.
Thirty-seven patients with active and 11 with treated CD, 40 healthy controls and 9 disease controls (Crohn's disease patients) were enrolled.
Several genes were differentially expressed in CD patients versus controls, but the analysis of each single gene did not provided a comprehensive picture. A multivariate discriminant analysis showed that the expression of 5 genes in intestinal mucosa accounted for 93% of the difference between CD patients and controls. We then applied the same approach to PBMs, on a training set of 20 samples. The discriminant equation obtained was validated on a testing cohort of 10 additional cases and controls, and we obtained a correct classification of all CD cases and of 91% of the control samples. We applied this equation to treated CD patients and to disease controls and obtained a discrimination of 100%.
The combined expression of 4 genes allows one to discriminate between CD patients and controls, and between CD patients on a gluten-free diet and disease controls. Our results contribute to the understanding of the complex interactions among CD-associated genes, and they may represent a starting point for the development of a molecular diagnosis of celiac disease.
乳糜泻（CD）是一种由麸质摄入引起的多因素自身免疫性疾病，易患个体存在遗传易感性。尽管技术不断进步，但 CD 的诊断仍然基于 50 年前的十二指肠活检。在这项研究中，我们分析了患者和对照者小肠活检组织中与 CD 相关的基因表达，以探讨 CD 患者表达谱的多变量途径。然后，我们使用多变量判别分析，评估这些基因在患者和对照者外周血单核细胞（PBM）中的表达谱是否存在差异。
37 例活动性 CD 患者和 11 例治疗后 CD 患者、40 名健康对照者和 9 名疾病对照者（克罗恩病患者）入组。
与对照组相比，CD 患者中有多个基因表达存在差异，但对每个单个基因的分析并未提供全面的信息。多变量判别分析显示，肠道黏膜中 5 个基因的表达差异解释了 CD 患者与对照组之间 93%的差异。我们随后将相同的方法应用于 PBM，在一个 20 例样本的训练集上进行。获得的判别方程在 10 例额外病例和对照者的测试队列中进行验证，我们正确地分类了所有 CD 病例和 91%的对照样本。我们将该方程应用于治疗后的 CD 患者和疾病对照者，得到了 100%的区分率。
4 个基因的联合表达可以区分 CD 患者和对照组，以及无麸质饮食的 CD 患者和疾病对照组。我们的研究结果有助于理解 CD 相关基因之间的复杂相互作用，并且可能为乳糜泻的分子诊断提供一个起点。
