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Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation (METHYLATION)

ABSTRACT: Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation (METHYLATION)

PROVIDER: PRJNA762909 | ENA |

REPOSITORIES: ENA

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Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation

Project description:Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation

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Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation (METHYLATION)

Project description:The inflammatory response to surgery is essential for healing and recovery, however hyperinflammation and altered immune competence increases the risk of inflammation mediated complications. We hypothesised that, in some patients, a state of postoperative systemic inflammatory dysregulation (PSID) exists increasing the risk or infection and sepsis, and that this will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. In this study we utilised phenotypic extremes of postoperative plasma C-reactive protein levels to define PSID, which manifested clinically in significantly higher rates of sepsis, complications and longer hospital stays following major abdominal surgery. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression confirms that dysregulation is mediated at multiple levels within specific gene sets and hence, non-specific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.

2021-09-17 | GSE184047 | GEO

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Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation

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Serum Peptidomic Profiling Reveals Systemic JAK-STAT and PI3K-Akt Dysregulation in Feline Chronic Gingivostomatitis

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Project description:Background and Aims: Celiac disease (CeD) is an autoimmune disease triggered by dietary gluten in genetically predisposed individuals. Deamidation of gluten peptides by the CeD autoantigen and enzyme transglutaminase 2 (TG2) is central to the pathogenesis of CeD. Inhibition of TG2 with the specific inhibitor ZED1227 effectively prevents gluten-induced histological damage in CeD patients. Here we aimed to explore the blood DNA methylomic changes in ZED1227-treated CeD patients undergoing a gluten challenge. Results: Drug treatment revealed consistent patterns suggesting normalization of the DNA methylome indicating that ZED1227 attenuated the systemic responses to gluten challenge. Conclusions: These findings provide evidence that ZED1227 can significantly prevent the gluten-induced CeD-associated systemic changes. Clinical trial: EudraCT 2017-002241-30

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