Discipline of Biomedical Sciences, School of Science and Technology, University of New England, Armidale, New South Wales, Australia.
Hunter New England Area Health Service, Tamworth, New South Wales, Australia.
J Gastroenterol Hepatol. 2019 Jan;34(1):169-177. doi: 10.1111/jgh.14369. Epub 2018 Jul 31.
The diagnosis of celiac disease autoimmune pathology relies on the subjective histological assignment of biopsies into Marsh score categories. It is hypothesized that Marsh score categories have unique gene expression signatures. The aims were as follows: first, to develop a celiac disease quantitative reverse transcription-polymerase chain reaction (RT-PCR) array; second, define gene expression signatures associated with Marsh score categories; and third, develop equations that classify biopsies into Marsh score categories and to monitor the efficacy of patient treatment.
Gene targets for inclusion in the celiac RT-PCR (qRT-PCR) array were identified using systematic analysis of published celiac transcriptomic data. The array was used to assess the gene expression associated with histological changes in duodenal biopsies obtained from adult patients. Finally, Marsh score classification equations were defined using discriminant analysis.
The array contained 87 genes. The expression of 26 genes were significantly (p < 0.06) associated with the discrete Marsh score categories. As the Marsh score pathology of biopsies increased, there was a progression of innate immune gene expression through adaptive Th1-specific gene expression with a concurrent decrease in intestinal structural gene expression in high Marsh score samples. These 26 genes were used to define classification equations that accounted for 99% of the observed experimental variation and which could classify biopsies into Marsh score categories and monitor patient treatment progression.
This proof-of-concept study successfully developed a celiac RT-PCR array and has provided evidence that discriminant equations defined using gene expression data can objectively and accurately classify duodenal biopsies into Marsh score categories.
乳糜泻自身免疫病理学的诊断依赖于对活检进行主观的 Marsh 评分分类。假设 Marsh 评分分类具有独特的基因表达特征。本研究的目的如下：首先，开发乳糜泻定量逆转录-聚合酶链反应（qRT-PCR）阵列；其次，定义与 Marsh 评分分类相关的基因表达特征；最后，开发将活检分类为 Marsh 评分分类的方程，并监测患者治疗的疗效。
使用发表的乳糜泻转录组数据的系统分析，确定纳入乳糜泻 qRT-PCR（qRT-PCR）阵列的基因靶标。该阵列用于评估从成年患者获得的十二指肠活检组织学变化相关的基因表达。最后，使用判别分析定义 Marsh 评分分类方程。
该阵列包含 87 个基因。26 个基因的表达与离散的 Marsh 评分分类显著相关（p<0.06）。随着活检 Marsh 评分病理学的增加，固有免疫基因表达通过适应性 Th1 特异性基因表达进行了发展，同时在高 Marsh 评分样本中肠结构基因表达下降。这 26 个基因用于定义分类方程，这些方程解释了 99%的观察到的实验变异，可以将活检分类为 Marsh 评分分类，并监测患者治疗进展。
这项概念验证研究成功地开发了乳糜泻 qRT-PCR 阵列，并提供了证据，即使用基因表达数据定义的判别方程可以客观、准确地将十二指肠活检分类为 Marsh 评分分类。
