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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE191331 | GEO | 2022/07/26

REPOSITORIES: GEO

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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease [methylation]

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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease

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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease [methylation]

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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease [RNA-Seq]

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A multi-omics approach to understand and predict therapeutic success of anti-TNF and anti-integrin agents in inflammatory bowel disease

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Project description:Purpose of the reviewThis review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD).Recent findingsSeveral real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.

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Anti-TNF-? Therapy Suppresses Proinflammatory Activities of Mucosal Neutrophils in Inflammatory Bowel Disease.

Project description:Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF-? mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF-? mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF-? therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF-? mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-?. These data indicate that TNF-? plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF-? modulates intestinal homeostasis through balancing immune responses of neutrophils.

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NAMPT and NAPRT serum levels predict response to anti-TNF therapy in inflammatory bowel disease.

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