scholarly journals Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3589
Author(s):  
Yasser Morsy ◽  
Nathalie Brillant ◽  
Yannick Franc ◽  
Michael Scharl ◽  
Marcin Wawrzyniak ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gene Locus ◽  
Intestinal Inflammation ◽  
Severe Disease ◽  
Mrna Levels ◽  
Disease Course ◽  
Risk Gene ◽  
Inflammatory Bowel ◽  
The Impact

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.

scholarly journals Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1787-1795 ◽  
Author(s):  
Mariana Ferreira-Duarte ◽  
Maria Manuela Estevinho ◽  
Margarida Duarte-Araújo ◽  
Fernando Magro ◽  
Manuela Morato
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Biologic Drugs ◽  
Multifunctional Protein ◽  
Expression Activity ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.

High and low body mass index may predict severe disease course in children with inflammatory bowel disease

2018 ◽  
Vol 53 (6) ◽  
pp. 708-713 ◽  
Author(s):  
Anat Yerushalmy-Feler ◽  
Amir Ben-Tov ◽  
Yael Weintraub ◽  
Achiya Amir ◽  
Tut Galai ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Inflammatory Bowel Disease ◽  
Body Mass ◽  
Bowel Disease ◽  
Severe Disease ◽  
Disease Course ◽  
Low Body Mass Index ◽  
Inflammatory Bowel

scholarly journals Inflammatory Bowel Disease Patients’ Perspectives during COVID-19 Pandemic: Results from a Portuguese Survey

2021 ◽  
pp. 1-9
Author(s):  
Joana Branco Revés ◽  
Catarina Frias-Gomes ◽  
Bárbara Morão ◽  
Catarina Nascimento ◽  
Carolina Palmela ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immunosuppressive Therapy ◽  
Bowel Disease ◽  
Severe Disease ◽  
Professional Life ◽  
Professional Activity ◽  
Biologic Treatment ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
The Impact

<b><i>Introduction:</i></b> Patients with inflammatory bowel disease (IBD) do not seem to be at increased risk of infection by SARS-CoV-2, but there is a concern whether immunosuppressive therapy may be associated with more severe disease. Several clinical practice recommendations have been published to help guide IBD care during the COVID-19 pandemic. Nonetheless, few studies have addressed patients’ perspectives and fears. We aimed to evaluate Portuguese IBD patients’ perspectives on the clinical management of their disease during the SARS-CoV-2 pandemic as well as the impact on their professional life. <b><i>Methods:</i></b> An anonymous electronic survey was created using REDCap and was distributed by the Portuguese Association of Inflammatory Bowel Disease (APDI) between May and August 2020. Patients’ perspectives on immunosuppressive therapy, disease management, interaction with gastroenterology departments, and the impact of the pandemic in their professional life were assessed. Patients’ proposals to improve medical care were also evaluated. Descriptive analysis and logistic regression were performed. <b><i>Results:</i></b> A total of 137 participants answered the survey (79.6% females, mean age 41.7 ± 12.1 years). Although having IBD and receiving treatment with immunosuppressors (thiopurines, steroids, or biologics) were considered promotors of anxiety, most patients (85.4%) agreed that disease remission was a priority and only a minority of patients interrupted their treatment during the pandemic. In multivariate analysis, active disease, biologic treatment, and use of corticosteroids in the last 3 months were perceived by the patients as high-risk features for increased risk of SARS-Cov-2 infection and more severe disease. Fifty-nine patients (44%) believed that their follow-up was influenced by the pandemic and only 58.8% felt that they had the opportunity to discuss their therapeutic options with their doctor. Sixty-three patients (46.0%) were working from home during the pandemic, although this decision was related to IBD and immunosuppressive therapy in only 36.5 and 39.7% of the cases, respectively. Areas where care could have been improved during the pandemic were identified by patients, namely enhancement of the communication with IBD professionals, conciliation of telemedicine with face-to-face appointments, and facilitation of the interaction between patients and employers. <b><i>Conclusion:</i></b> Most patients agreed that maintaining IBD remission is crucial, and only a minority of the patients stopped their treatment as per their own initiative. IBD status only had a small influence on patients’ professional activity during the COVID-19 outbreak, with most changes being related to the pandemic itself.

scholarly journals The Impact of PPARγGenetic Variants on IBD Susceptibility and IBD Disease Course

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jessica Mwinyi ◽  
Christa Grete-Wenger ◽  
Jyrki J. Eloranta ◽  
Gerd A. Kullak-Ublick
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Bowel Disease ◽  
Genetic Variants ◽  
Bioinformatic Analysis ◽  
Healthy Controls ◽  
Disease Course ◽  
Colon Inflammation ◽  
Inflammatory Bowel ◽  
The Impact

PPARγ is a nuclear receptor that regulates numerous pathways including cytokine expression and immune responses and plays an important role in controlling colon inflammation. We aimed at determining the occurringPPARγ SNPs, at predicting the haplotypes, and at determining the frequency outcome in inflammatory bowel disease (IBD) patients in comparison with healthy controls. We determined genetic variants in the coding exons and flanking intronic sequences of theNR1C3gene in 284 IBD patients and 194 controls and predictedNR1C3haplotypes via bioinformatic analysis. We investigated whether certainNR1C3variants are associated with susceptibility to IBD or its disease course. None of the detected 22NR1C3variants were associated with IBD. Two variants with allelic frequencies over 1% were included in haplotype/diplotype analyses. None of theNR3C1haplotypes showed association with IBD development or disease course. We conclude thatNR1C3haplotypes are not related to IBD susceptibility or IBD disease activity.

scholarly journals The Unique Disease Course of Children with Very Early onset-Inflammatory Bowel Disease

2019 ◽  
Author(s):  
Judith R Kelsen ◽  
Maire A Conrad ◽  
Noor Dawany ◽  
Trusha Patel ◽  
Rawan Shraim ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Targeted Therapy ◽  
Bowel Disease ◽  
Early Onset ◽  
Severe Disease ◽  
Disease Course ◽  
Poor Growth ◽  
Study Objective ◽  
Inflammatory Bowel

Abstract Background Insight into the pathogenesis of very early onset-inflammatory bowel disease (VEO-IBD) has expanded through the identification of causative monogenic defects detected in a subset of patients. However, the clinical course of this population remains uncertain. The study objective is to determine whether VEO-IBD is associated with more severe disease, defined as increased surgical intervention and growth failure, than older pediatric IBD. Secondary outcomes included therapeutic response and hospitalizations. Methods Subjects with IBD diagnosed younger than 6 years old (VEO-IBD) were compared with children diagnosed 6 to 10 (intermediate-onset) and older than 10 years of age (older-onset IBD). Metadata obtained from the medical record included age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions. Length of follow-up was at least 1 year from diagnosis. Results There were 229, 221, and 521 subjects with VEO, intermediate-onset, and older-onset IBD, respectively. Very early onset-inflammatory bowel disease subjects underwent more diverting ileostomies (P < 0.001) and colectomies (P < 0.001) than the older children. There was less improvement in weight- and height-for-age Z scores during the follow-up period in subjects with VEO-IBD. Additionally, subjects with VEO-IBD had higher rates of medication failure at 1 year and were more frequently readmitted to the hospital. Targeted therapy was successfully used almost exclusively in VEO-IBD. Conclusion Patients with VEO-IBD can have a more severe disease course with increased surgical interventions and poor growth as compared with older-onset IBD patients. Further, VEO-IBD patients are more likely to be refractory to conventional therapies. Strategies using targeted therapy in these children can improve outcome and, in some cases, be curative.

scholarly journals The Impact of Farnesoid X Receptor Activation on Intestinal Permeability in Inflammatory Bowel Disease

2012 ◽  
Vol 26 (9) ◽  
pp. 631-637 ◽  
Author(s):  
Maja Stojancevic ◽  
Karmen Stankov ◽  
Momir Mikov
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Tract ◽  
Intestinal Inflammation ◽  
Strong Support ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
The Impact

The most important function of the intestinal mucosa is to form a barrier that separates luminal contents from the intestine. Defects in the intestinal epithelial barrier have been observed in several intestinal disorders such as inflammatory bowel disease (IBD). Recent studies have identified a number of factors that contribute to development of IBD including environmental triggers, genetic factors, immunoregulatory defects and microbial exposure. The current review focuses on the influence of the farnesoid X receptor (FXR) on the inhibition of intestinal inflammation in patients with IBD. The development and investigation of FXR agonists provide strong support for the regulatory role of FXR in mucosal innate immunity. Activation of FXR in the intestinal tract decreases the production of proinflammatory cytokines such as interleukin (IL) 1-beta, IL-2, IL-6, tumour necrosis factor-alpha and interferon-gamma, thus contributing to a reduction in inflammation and epithelial permeability. In addition, intestinal FXR activation induces the transcription of multiple genes involved in enteroprotection and the prevention of bacterial translocation in the intestinal tract. These data suggest that FXR agonists are potential candidates for exploration as a novel therapeutic strategy for IBD in humans.

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