Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/26246
Title: Celiac disease gene expression data can be used to classify biopsies along the Marsh score severity scale
Contributor(s): Charlesworth, Richard P G  (author)orcid ; Agnew, Linda L  (author)orcid ; Scott, David R (author); Andronicos, Nicholas M  (author)orcid 
Publication Date: 2019
Early Online Version: 2018-07-02
DOI: 10.1111/jgh.14369
Handle Link: https://hdl.handle.net/1959.11/26246
Abstract: Background and Aim: 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. Methods: 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. Results: 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. Conclusions: 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.
Publication Type: Journal Article
Source of Publication: Journal of Gastroenterology and Hepatology, 34(1), p. 169-177
Publisher: Wiley-Blackwell Publishing Asia
Place of Publication: Australia
ISSN: 1440-1746
0815-9319
Fields of Research (FoR) 2008: 100402 Medical Biotechnology Diagnostics (incl. Biosensors)
110316 Pathology (excl. Oral Pathology)
110703 Autoimmunity
Fields of Research (FoR) 2020: 320403 Autoimmunity
320803 Systems physiology
320220 Pathology (excl. oral pathology)
Socio-Economic Objective (SEO) 2008: 920105 Digestive System Disorders
920108 Immune System and Allergy
Socio-Economic Objective (SEO) 2020: 200105 Treatment of human diseases and conditions
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article
School of Science and Technology

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