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E31b504f-9004-4bcc-a718-194fd81a0619 - samples

ABSTRACT: This dataset contains PBMC genome-wide RNAseq reads from 21 samples and one expression matrix file after alignment and aggregation of the 21 samples. The samples are case-control drawn on day 6 from long-term GFD treated CD patients after 3 day oral gluten challenge, on day 0 from patient controls on long-term GFD treatment, and on day 6 from 4 week GFD treated healthy controls after 3 day oral gluten challenge.

PROVIDER: EGAD00001006655 | EGA |

REPOSITORIES: EGA

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Project description:Coeliac disease is a small intestinal disorder caused by an abarrent immune response towards dietary gluten due to activation of pro-inflammatory gluten specific CD4+ T cells. Histological evaluation and classification of gluten induced musosal changes is part of the diagnostic work up. of adults. The kinetics of mucosal recovery following commencesment of a gluten free diet (disease remission) and the degree of mucosal changes induced by gluten reintroduction (gluten challenge) varies between patients. Also, patients classified with similar clinical and histological disease remission, can develop different degree of mucosal damage following the same gluten challenge regime. This variation poses a challenge for the interpretation of gluten induced mucosal changes both in a diagnostic and clinical trial settings. In this study, we have analysed material from small intestinal biopsies collected from 19 treated coeliac disease patients before and after completion of a 14-day oral gluten challenge. These patients are part of a previoslpreviouslyu described study where all patients were in clinical and mucosal remission at baseline but only some patients developed histological changes in the mucosa in response to gluten. We have performed shotgun LC-MSMS analysis and label-free quantification of total gut tissue and from laser capture microdissected epithelial cell layer samples. We found that differences in tissue proteome expression could separate patients as responders and non-responders to the gluten challenge. Patients whoich responded strongly to gluten , had signs of gut inflammation already at baseline, supported by presence of low-level blood inflammatory parameters and a slight increase in numbers of gluten-specific CD4+ T cells at baseline. Our proteomics analysis demonstrated baseline differences in gut tissue state between patients that were not evident from routine clinical and histological evaluation. These baseline differences likely explains why some patients respond more strongly to gluten challenge than others.

Project description:Oral polymorphonuclear neutrophils (oPMNs) are essential for the maintenance of oral health. Functionally active oPMNs have been described in oral health, gingivitis and periodontitis. Interestingly, recent evidence showed that oPMNs from chronic periodontitis patients have a similar functional and reactivity pattern compared to oPMNs from healthy subjects. However, it remains unknown whether oPMNs respond to the initiation and resolution of gingival inflammation. Therefore, this study aimed to evaluate the oPMNs’ transcriptional responses during the initiation and resolution of an experimentally induced gingivitis. Oral rinses were obtained from 8 subjects at 4 different time points during the experiment for the isolation of oPMNs; day 0 (baseline), day 9 (during gingivitis challenge), day 14 (end of the challenge) and day 21 (resolution). Transcriptome of oPMNs was determined by RNAsequencing. Differentially expressed genes (DEGs) was selected at P<0.01 level, and evaluated for pathway regulation at different time points using Ingenuity Pathway Analysis suite. During the gingivitis challenge, dental plaque levels and gingival bleeding levels were significantly increased at day 14 compared to baseline. Transcriptome analysis indicate four major clusters of DEGs, which consisted of a group of 256 initial response DEGs (day 9 only), 221 late response DEGs (day 14 only), 53 persistent response DEGs (consistent at day 9 and day 14), and a group of 524 DEGs showing response only after the gingivitis challenge (day 21 only). Pathway analysis of the initial response DEGs showed their involvement in many immune regulatory pathways (interleukin signaling, reactive oxygen species processes and granulocyte adhesion and diapedesis). Late responding DEGs mainly showed activation of signaling pathways and phagosome formation as part of the phagocytosis process, whereas DEGs at day 21 were involved in epithelial adherence signaling and other miscellaneous related signaling pathways. This study showed that oPMNs have specific expression profiles during the development and resolution of experimental gingivitis. Even though, the specific observed pathways were not identical within each time point, the altered pathways indicate PMN responses in general and suggests an immunomodulatory role for the oPMNs. The oPMNs may therefore play a co-controlling part in the initiation and resolution of gingival inflammation.

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E31b504f-9004-4bcc-a718-194fd81a0619 - samples

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