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The Role of the Innate and Adaptive Immune System in Pediatric Inflammatory Bowel Disease

Denson, Lee A. MD

doi: 10.1097/MIB.0b013e318281f590
Basic Review Article

Abstract: Recent translational studies have provided new insights into the pathogenesis of pediatric-onset inflammatory bowel disease. Registry studies have identified distinct clinical phenotypes with increasing age of onset; this has led to a revision of the clinical phenotyping system, now termed the Paris classification system. It is recognized that there are infantile (age, <1 years), very early onset (VEO) (age, 1–10 years), and early onset (age, 10–17 years) forms of disease. Rare genetic mutations affecting antimicrobial and anti-inflammatory pathways have been discovered in infantile and VEO forms, although genetic pathways identified in early onset disease have been similar to adult-onset inflammatory bowel disease. An increasing incidence in the infantile and VEO forms has suggested an important environmental influence. This is likely ultimately expressed through alterations in the enteric flora (dysbiosis) and dysregulated immune responses to the flora, which are recognized as a critical trigger for mucosal inflammation. These data should ultimately guide new pathogenic models of disease, which will inform both therapy in individual patients and disease prevention in their at-risk family members.

Article first published online 22 May 2013

Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Reprints: Lee A. Denson, MD, MLC 2010, 3333 Burnet Avenue, Cincinnati, OH 45229 (e-mail:

Supported in part by the National Institutes of Health grant (R01 DK078683).

The authors have no conflicts of interest to disclose.

Received October 30, 2012

Accepted November 19, 2012

© Crohn's & Colitis Foundation of America, Inc.
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