Inflammatory Bowel Disease in Primary Immunodeficiencies

Abstract

Purpose of review: Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease.

Recent findings: The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.

Keywords: Crohn’s colitis; Early-onset IBD; Monogenic IBD; Ulcerative colitis.

Fig. 1

Duodenal biopsy of a 5-year-old male with confirmed ZBTB24 mutation. Mutations in ZBTB24 are associated with immunodeficiency–centromeric instability–facial anomalies syndrome. The rate of diarrhea in this syndrome is high, but the prevalence of IBD is not known. These biopsies show several atypical features for IBD. (a) The lamina propria is relatively hypocellular with few plasma cells in loose aggregates (hematoxylin–eosin). (b) The small bowel demonstrates villous blunting (hematoxylin–eosin). (c) The plasma cells have been stained with CD79a to demonstrate their paucity in the small bowel, compared to (d) a normal control stained for CD79a