scholarly journals Profiling Non-Coding RNA Levels With Clinical Classifiers in Pediatric Crohn’s Disease

2020 ◽  
Author(s):  
Ranjit S. Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background: Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods: Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) >2 and FDR < 0.05 after multiple test corrections. Results: In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up.Conclusions: We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Profiling non-coding RNA levels with clinical classifiers in pediatric Crohn’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ranjit Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) > 2 and FDR < 0.05 after multiple test corrections. Results In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up. Conclusions We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? “The Pro Position”

2021 ◽  
pp. 1-6
Author(s):  
Neil O’Moráin ◽  
Jayne Doherty ◽  
Roisin Stack ◽  
Glen A. Doherty
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Injury ◽  
Mucosal Healing ◽  
Inflammatory Disorder ◽  
Stricture Formation ◽  
Chronic Inflammatory Disorder ◽  
Non Invasive ◽  
Appropriate Treatment ◽  
Bull's Eye

<b><i>Background:</i></b> Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. <b><i>Summary:</i></b> Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. <b><i>Key Messages:</i></b> Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

scholarly journals Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn’s Disease: An Up-To-Date Review

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 563
Author(s):  
Gaetano Gallo ◽  
Vincenzo Tiesi ◽  
Serena Fulginiti ◽  
Gilda De Paola ◽  
Giuseppina Vescio ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Negative Impact ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Entire Gastrointestinal Tract

Crohn’s Disease (CD) is a chronic inflammatory disorder that potentially involves the entire gastrointestinal tract. Perianal fistulizing CD (pCD) is a serious and frequent complication associated with significant morbidities and a heavy negative impact on quality of life. The aim of CD treatment is to induce and maintain disease remission and to promote mucosal repair. Unfortunately, even the best therapeutic regimens in pCD do not have long-term efficacy and cause a significant number of side effects. Therefore, it is mandatory to study new therapeutical options such as the use of mesenchymal stromal cells (MSCs). These cells promote tissue repair via the induction of immunomodulation. The present review aims to analyze the existing updated scientific literature on MSCs adoption in the treatment of pCD to evaluate its efficacy and safety and to compare the use of bone marrow and adipose tissue derived MSCs, type of administration, and dose required for recovery.

scholarly journals Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn’s Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Andressa Coope ◽  
Lívia Bitencourt Pascoal ◽  
Francesca Aparecida Ramos da Silva ◽  
José Diego Botezelli ◽  
Maria de Lourdes Setsuko Ayrizono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Signaling Pathways ◽  
Intestinal Mucosa ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Mesenteric Adipose Tissue ◽  
Immune Mediated ◽  
First Time

Crohn’s disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFαlevel were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.

scholarly journals Journey through Crohn’s Disease Complication: From Fistula Formation to Future Therapies

2021 ◽  
Vol 10 (23) ◽  
pp. 5548
Author(s):  
Federica Rubbino ◽  
Luana Greco ◽  
Alessio di Cristofaro ◽  
Federica Gaiani ◽  
Stefania Vetrano ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Fistula Formation ◽  
Surgical Approaches ◽  
Molecular Characteristics ◽  
Inflammatory Disorder ◽  
Mesenchymal Transition ◽  
Chronic Inflammatory Disorder ◽  
Increased Risk

Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phenotypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies. At present, the most accredited theory for the formation of CD-related fistula identifies the epithelial-to-mesenchymal transition (EMT) as the driving force. It has been well recognized that CD carries an increased risk of malignancy, particularly mucinous adenocarcinoma is often associated with long-standing fistula in CD patients. Despite the availability of multiple treatment options, perianal fistulizing CD represents a therapeutic challenge and is associated with an important impact on patients’ quality of life. To date, the most effective management is multidisciplinary with the cooperation of gastroenterologists, surgeons, radiologists, and nutritionists and the best recommended treatment is a combination of medical and surgical approaches.

XI. Novel mouse models to study pathogenic mechanisms of Crohn's disease

2000 ◽  
Vol 278 (5) ◽  
pp. G665-G669 ◽  
Author(s):  
Theresa T. Pizarro ◽  
Kristen O. Arseneau ◽  
Fabio Cominelli
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mouse Models ◽  
Intestinal Inflammation ◽  
The United States ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Therapeutic Modalities ◽  
Genetically Manipulated ◽  
Chronic Intestinal Inflammation

Crohn's Disease (CD) affects more than 500,000 individuals in the United States and represents the second most common chronic inflammatory disorder after rheumatoid arthritis. Although major advances have been made in defining the basic mechanisms underlying chronic intestinal inflammation, the precise etiopathogenesis of CD remains unknown. We have recently characterized two novel mouse models of enteritis that express a CD-like phenotype, namely the TNF ΔARE model of tumor necrosis factor (TNF) overexpression and the SAMP1/Yit model of spontaneous ileitis. The unique feature of these models is that they closely resemble CD for location and histopathology. These genetically manipulated new models of intestinal inflammation offer a powerful tool to investigate potential causes of human disease and may allow the development of novel disease-modifying therapeutic modalities for the treatment of CD.

scholarly journals Roles of IL-17A and IL-23 in the Pathogenesis of Ulcerative Colitis and Crohn’s Disease

2021 ◽  
pp. 2526-2535
Author(s):  
Sarah S. Abdul-Hussein ◽  
Ekhlass N. Ali ◽  
Nawal M. F. Alkhalidi ◽  
Neihaya H. Zaki ◽  
Ali H. Ad'hiah
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Smoking Status ◽  
Serum Levels ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
History Of ◽  
Disease Extension

     Inflammatory bowel disease (IBD) is a chronic inflammatory disorder,  the etiology and pathogenesis of which have been suggested to be influenced by cytokines. Two main clinical types of IBD are recognized, namely ulcerative colitis (UC) and Crohn's disease (CD). The present study examined serum levels of two cytokines (IL-17A and IL-23) in 60 IBD patients (30 UC and 30 CD) and 30 healthy controls. The levels were correlated with age, gender, cigarette-smoking status, disease duration, family history, disease extension, symptoms, extra-intestinal manifestations, and medication. The results depicted that IL-17A level was significantly higher in UC and CD patients compared to control (45.2 ± 23.3 and 47.5 ± 34.4 vs. 15.6 ± 7.5 pg/ml, respectively; p < 0.001). Serum level of IL-23 was similarly increased in UC and CD patients compared to control (64.1± 23.7 and 62.5 ± 27.3 vs. 25.2 ± 11.1 pg/ml, respectively). However, the level of both cytokines showed no significant variation between UC and CD patients (p = 0.713 and 0.777, respectively). Distributing UC and CD patients into subgroups according to some characteristics revealed that IL-17A level was significantly increased in UC male compared to female patients (57.3 ± 18.2 vs. 34.5 ± 22.5 pg/ml; p = 0.005). It was also significantly increased in smoker UC patients compared with non-smoker patients (51.9 ± 19.4 vs. 31.6 ± 25.5 pg/ml; p = 0.022). Smoker CD patients also showed a significantly increased level of IL-23 compared to non-smoker patients (72.7 ± 28.5 vs. 52.2 ± 22.6 pg/ml; p = 0.038). In the case of family history, IL-23 level was significantly decreased in UC patients with a family history of IBD compared to CD patients with a family history (84.5 ± 24.3 vs. 50.4 ± 17.0 pg/ml.; p = 0.042). In conclusion, the present data suggest a role for IL-17A and IL-23 in the etiology and pathogenesis of UC and CD.

scholarly journals Capsule Endoscopy in Crohn’s Disease—From a Relative Contraindication to Habitual Monitoring Tool

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1737
Author(s):  
Adi Lahat ◽  
Ido Veisman
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Capsule Endoscopy ◽  
Invasive Procedure ◽  
Disease Diagnosis ◽  
Inflammatory Disorder ◽  
Disease Extent ◽  
Chronic Inflammatory Disorder ◽  
Relative Contraindication

Crohn’s disease (CD) is a chronic inflammatory disorder that may involve the gastrointestinal tract from the mouth to the anus. Habitual disease monitoring is highly important during disease management, aiming to identify and treat disease exacerbations, in order to avoid immediate and future complications. Currently, ilio-clonoscopy is the gold standard for mucosal assessment. However, the procedure is invasive, involves sedation and allows for visualization of the colon and only a small part of the terminal ileum, while most of the small bowel is not visualized. Since CD may involve the whole length of the small bowel, the disease extent might be underestimated. Capsule endoscopy (CE) provides a technology that can screen the entire bowel in a non-invasive procedure, with minimal side effects. In recent years, this technique has gained in popularity for CD evaluation and monitoring. When CE was first introduced, two decades ago, the fear of possible capsule retention in the narrowed inflamed bowel lumen limited its use in CD patients, and a known CD located at the small bowel was even regarded as a relative contraindication for capsule examination. However, at present, as experience using CE in CD patients has accumulated, this procedure has become one of the accepted tools for disease diagnosis and monitoring. In our current review, we summarize the historic change in the indications and contraindications for the usage of capsule endoscopy for the evaluation of CD, and discuss international recommendations regarding CE’s role in CD diagnosis and monitoring.

Clinical profile and predictors of disease behavior and surgery in Indian patients with Crohn's disease

2013 ◽  
Vol 32 (3) ◽  
pp. 184-189 ◽  
Author(s):  
Ashish Goel ◽  
Amit Kumar Dutta ◽  
Anna B. Pulimood ◽  
Anu Eapen ◽  
Ashok Chacko
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Profile ◽  
Indian Patients ◽  
Disease Behavior

scholarly journals Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn’s Disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julie E. Horowitz ◽  
Neil Warner ◽  
Jeffrey Staples ◽  
Eileen Crowley ◽  
Nehal Gosalia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Function ◽  
Early Onset ◽  
Low Frequency ◽  
Mendelian Inheritance ◽  
Clinical Population ◽  
Mendelian Disease ◽  
Recessive Inheritance ◽  
Pediatric Onset

AbstractInflammatory bowel disease (IBD), clinically defined as Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified, results in chronic inflammation of the gastrointestinal tract in genetically susceptible hosts. Pediatric onset IBD represents ≥ 25% of all IBD diagnoses and often presents with intestinal stricturing, perianal disease, and failed response to conventional treatments. NOD2 was the first and is the most replicated locus associated with adult IBD, to date. However, its role in pediatric onset IBD is not well understood. We performed whole-exome sequencing on a cohort of 1,183 patients with pediatric onset IBD (ages 0–18.5 years). We identified 92 probands with biallelic rare and low frequency NOD2 variants accounting for approximately 8% of our cohort, suggesting a Mendelian inheritance pattern of disease. Additionally, we investigated the contribution of recessive inheritance of NOD2 alleles in adult IBD patients from a large clinical population cohort. We found that recessive inheritance of NOD2 variants explains ~ 7% of cases in this adult IBD cohort, including ~ 10% of CD cases, confirming the observations from our pediatric IBD cohort. Exploration of EHR data showed that several of these adult IBD patients obtained their initial IBD diagnosis before 18 years of age, consistent with early onset disease. While it has been previously reported that carriers of more than one NOD2 risk alleles have increased susceptibility to Crohn’s Disease (CD), our data formally demonstrate that recessive inheritance of NOD2 alleles is a mechanistic driver of early onset IBD, specifically CD, likely due to loss of NOD2 protein function. Collectively, our findings show that recessive inheritance of rare and low frequency deleterious NOD2 variants account for 7–10% of CD cases and implicate NOD2 as a Mendelian disease gene for early onset Crohn’s Disease.

Sign in / Sign up

Export Citation Format

Share Document