Abstract
ObjectiveIn 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.DesignBy 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.ResultsPediatric 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.ConclusionThe 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.
Highlights
Inflammatory bowel disease (IBD) is known as a chronic inflammatory disease of the intestine
Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls
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
Summary
Inflammatory bowel disease (IBD) is known as a chronic inflammatory disease of the intestine. Multiple treatment options have been used to control inflammation, to date no curative interventions have been described. The major aim of treatment is the induction and preservation of clinical remission. Differences in phenotype, medication responsiveness and associated genetic polymorphisms, illustrate that IBD patients represent a heterogeneous group that may need a novel classification beyond that of Crohn’s disease (CD) and ulcerative colitis (UC). Genotype, RNA expression, demographic parameters and disease location may help to discriminate subsets within this patient population. 15% of all IBD cases have disease onset during childhood. [1] Given the distinct disease phenotype and associated pathological changes in children compared to adults, pediatric disease onset can be seen as a specific subset of IBD. 15% of all IBD cases have disease onset during childhood. [1] Given the distinct disease phenotype and associated pathological changes in children compared to adults, pediatric disease onset can be seen as a specific subset of IBD. [1,2,3,4]
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