Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission

Objective: In current clinical practice, optimal treatment of inflammatory bowel disease (IBD) aims at the induction and maintenance of clinical remission. Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to categorize patients with clinical remission into subsets with variable states of immune activation. Design: By using Affymetrix GeneChips, we analysed RNA gene expression profiles of peripheral blood leukocytes from pediatric IBD patients in clinical remission and controls. We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients. Results: Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls. We identified three clusters of IBD patients, each displaying specific expression profiles of IBD-associated genes. Conclusion: The expression of immune- and IBD-associated genes in peripheral blood leukocytes from pediatric IBD patients in clinical remission was different from healthy controls, indicating that sub-clinical immune mechanisms are still active during remission. As such, RNA profiling of peripheral blood may allow for non-invasive patient subclassification and new perspectives in treatment regimes of IBD patients in the future

The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

<div><p>Objective</p><p>In current clinical practice, optimal treatment of inflammatory bowel disease (IBD) aims at the induction and maintenance of clinical remission. Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to categorize patients with clinical remission into subsets with variable states of immune activation.</p><p>Design</p><p>By using Affymetrix GeneChips, we analysed RNA gene expression profiles of peripheral blood leukocytes from pediatric IBD patients in clinical remission and controls. We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.</p><p>Results</p><p>Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls. We identified three clusters of IBD patients, each displaying specific expression profiles of IBD-associated genes.</p><p>Conclusion</p><p>The expression of immune- and IBD-associated genes in peripheral blood leukocytes from pediatric IBD patients in clinical remission was different from healthy controls, indicating that sub-clinical immune mechanisms are still active during remission. As such, RNA profiling of peripheral blood may allow for non-invasive patient subclassification and new perspectives in treatment regimes of IBD patients in the future.</p></div

Use of exclusive enteral nutrition in paediatric Crohn's disease in The Netherlands

A six-week course of exclusive enteral nutrition (EEN) is recommended as first treatment in active paediatric Crohn's disease (CD). We aimed to assess short-term and long-term outcome of EEN, and to identify predictive factors of treatment success. The medical records of newly diagnosed paediatric CD patients initiating EEN as remission induction therapy between January 2008 and October 2011 were retrospectively studied. Treatment outcome was assessed using a previously described pattern recognition model. 77 CD patients (median age 13.9 years, 57% male) initiated a six-week course of EEN, combined with azathioprine maintenance treatment in 92%. Patients received EEN as either hyperosmolar sip feeds or polymeric formula by nasogastric tube. In patients completing a six-week course of EEN (n=58), complete remission was achieved in 71%, partial remission in 26%, and no response in 3%. Complete remission rates were higher in children presenting with isolated ileal/ileocaecal disease and malnutrition. Nineteen patients discontinued EEN before the intended treatment period due to worsening of symptoms (n=9) or adherence issues (n=10). Non-adherence occurred more often in older children, females, children from non-Dutch parents, and patients taking hyperosmolar sip feeds compared with polymeric formula by nasogastric tube. The likelihood of relapsing disease within the first year after EEN treatment was 59%. A six-week course of EEN is effective in newly diagnosed paediatric CD, with response rates that seem to be influenced by disease location and nutritional status, but not by type of formula. Non-adherence occurs frequently and limits the success of this treatment in everyday clinical practic

Atypical disease phenotypes in pediatric ulcerative colitis: 5-year analyses of the EUROKIDS Registry

Background: Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification. Methods: Information was collected from the EUROKIDS Registry, an inception cohort of untreated pediatric IBD patients undergoing evaluation at diagnosis. Patients with IBD-unclassified were excluded. Patients with isolated Crohn's colitis served as a control group. Results: Data from 898 pediatric patients (643 UC, 255 CD colitis) were included. Extensive or pancolitis was present in 77% of UC patients and macroscopic rectal sparing in 5%. Rectal sparing was inversely associated with age (mean age with rectal sparing 9.9 years vs. 11.8 without; P = 0.02). Upper gastrointestinal (UGI) involvement occurred in 4% of patients. Erosions in the stomach were present in 3.1% of children, but frank ulcerations in 0.4%; 0.8% of children had erosions or ulcerations limited to the esophagus or duodenum. The corresponding UGI involvement in Crohn's colitis was 22%. A cecal patch occurred in 2% of patients. Conclusions: Extensive disease and rectal sparing are age-dependent phenotypes in pediatric UC. Rectal sparing, cecal patch, backwash ileitis, and gastric erosions are not uncommon at diagnosis, while gastric ulcerations and erosions in the duodenum or esophagus are. Recognition of atypical phenotypes in pediatric-onset UC is crucial to prevent misclassification of IBD

Disease phenotype at diagnosis in pediatric Crohn's disease: 5-year analyses of the EUROKIDS Registry

Background: It has been speculated that pediatric Crohn's disease (CD) is a distinct disease entity, with probably different disease subtypes. We therefore aimed to accurately phenotype newly diagnosed pediatric CD by using the pediatric modification of the Montreal classification, the Paris classification. Methods: Information was collected from the EUROKIDS registry, a prospective, web-based registry of new-onset pediatric IBD patients in 17 European countries and Israel. When a complete diagnostic workup was performed (ileocolonoscopy, upper gastrointestinal [GI] endoscopy, small bowel imaging), CD patients were evaluated for ileocolonic disease extent, esophagogastroduodenal involvement, and jejunal/proximal ileal involvement. Disease behavior and the occurrence of granulomas were also analyzed. Results: In all, 582 pediatric CD patients could be classified according to the Paris classification. Isolated terminal ileal disease (+/- limited cecal disease) was seen at presentation in 16%, isolated colonic disease in 27%, ileocolonic disease in 53%, and isolated upper GI disease in 4% of patients. In total, 30% had esophagogastroduodenal involvement and 24% jejunal/proximal ileal disease. Patients with L2 disease were less likely to have esophagogastroduodenal involvement or stricturing disease than patients with L1 or L3 disease. Terminal ileal disease and stricturing disease behavior were more common in children diagnosed after 10 years of age than in younger patients. Granulomas were identified in 43% of patients. Conclusions: Accurate phenotyping is essential in pediatric CD, as this affects the management of individual patients. Disease phenotypes differ according to age at disease onset. The Paris classification is a useful tool to capture the variety of phenotypic characteristics of pediatric CD

Top canonical pathways Group A/B/C vs Control.

<p>Top canonical pathways Group A/B/C vs Control.</p

Top canonical pathways Group A/B/C vs Group and Controls.

<p>Top canonical pathways Group A/B/C vs Group and Controls.</p

Gene expression profiles of quiescent pediatric IBD patients.

<p>Global gene expression profiles of peripheral blood leukocytes were analysed using principal components analysis (PCA). Samples with higher similarity between gene expression profiles cluster more strongly together in the PCA space. Crohn’s disease (red) and ulcerative colitis (green) patients with quiescent disease are not different from each other and form a heterogeneous cluster that is distinct from controls (blue).</p