Pediatric Inflammatory Bowel Disease: from diagnosis to transition

The inflammatory bowel diseases (IBD) are chronic relapsing inflammatory disorders of the gastrointestinal tract, comprising Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U). CD is characterized by a transmural and often granulomatous inflammation that can involve any part of the gastrointestinal tract in a discontinuous manner, while UC is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon, without granulomas on biopsy, affecting the rectum and a variable extent of the colon in continuity. The term IBD-U is used for patients presenting with IBD restricted to the colon without the specific features of either CD or UC.2 Early-onset IBD represents a distinct disease entity with differences in disease type, disease location, disease behavior, gender preponderance, and genetically attributable risk compared with late-onset IBD. As in adults, treatment of early-onset IBD is aimed at inducing and maintaining remission, but special considerations are needed regarding optimal growth, pubertal development, and the transition period to adult care. A better understanding of the differences between early-onset and late-onset IBD will eventually lead to a better understanding of the pathogenesis of the disease. One of the limitations of studying pediatric IBD is however that a relatively small number of patients is available for study at one institution, which requires ongoing collaborations between many institutions. This thesis will present six (inter)national multicenter studies, a single-center pilot study and a review, which all focus on the unique clinical aspects of pediatric IBD, thereby complementing the relatively small body of literature on the diagnosis and treatment of children with IBD

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