Genomic and Immunologic Drivers of Very Early-Onset Inflammatory Bowel Disease. (May 2019)

• Record Type: Journal Article
• Authors: Conrad, Maire A; Kelsen, Judith R
• Is Part Of: Pediatric and developmental pathology. Volume 22:Number 3(2019)
• Page Start: 183
• Page End: 193
• Publication Date: 2019-05
• Subjects: very early-onset inflammatory bowel disease -- whole-exome sequencing -- immunodeficiency; Pediatric pathology -- Periodicals; Children -- Diseases -- Periodicals; Diagnosis, Laboratory -- Periodicals; Abnormalities, Human -- Periodicals; Child development -- Periodicals; Pediatrics -- Periodicals; 616.07
• DOI: 10.1177/1093526619834807
• Languages: English
• ISSNs: 1093-5266

Abstract

Purpose of Review: Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. However, a subset of patients with IBD diagnosed <6 years of age, known as very early-onset (VEO)-IBD, can be phenotypically and genetically distinct from older onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to the underlying genomic and immunologic drivers of disease, and the significant impact on our therapeutic decisions. Recent Findings: VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression, and poor response to most conventional therapies. This article will review some of the genetic findings in this population and the subsequent impact on therapy, with targeted approaches. Summary: Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. An integrated approach combining genetics, immunology, and traditional IBD evaluations can lead to the identification of causal defects that directly impact management. These strategies can also be employed in older onset refractory IBD.