Understanding very early onset inflammatory bowel disease (VEOIBD) in relation to inborn errors of immunity

Abstract

Inflammatory bowel diseases (IBD) are multifactorial diseases which are caused by the combination of genetic predisposition, exposure factors (environmental and dietary), immune status, and dysbiosis. IBD is a disease which presents at any age, ranging from newborns to the elderly. The youngest of the pediatric IBD population have a more unique presentation and clinical course and may have a different etiology. Very early onset IBD (VEOIBD) patients, designated as those diagnosed prior the age of 6, have distinct features which are more frequent in this patient population including increased incidence of monogenetic causes for IBD (0%-33% depending on the study). This proportion is increased in the youngest subsets, which is diagnosed prior to the age of 2. To date, there are approximately 80 monogenic causes of VEOIBD that have been identified and published. Many of these monogenic causes are inborn errors of immunity yet the majority of VEOIBD patients do not have an identifiable genetic cause for their disease. In this review, we will focus on the clinical presentation, evaluation, and monogenic categories which have been associated with VEOIBD including (1) Epithelial cell defects (2) Adaptive immune defects, (3) Innate Immune/Bacterial Clearance and Recognition defects, and (4) Hyperinflammatory and autoinflammatory disorders. We will highlight differential diagnosis of VEOIBD presentations, as well as evaluation and treatment, which will be helpful for those who study and care for VEOIBD patients outside of the pediatric gastroenterology field. This is a fast-moving field of research which has grown significantly based on knowledge that we gain from our patients. These scientific findings have identified novel mucosal biology pathways and will continue to inform our understanding of gastrointestinal biology.

Keywords: T cells; autoinflammatory process; epithelial cells; inflammatory bowel disease; monogenic; very early onset inflammatory bowel disease.

FIGURE 1

Evaluation of patients with very early onset inflammatory bowel disease. Created with Biorender.com.

FIGURE 2

Genes involved in monogenic causes of very early onset inflammatory bowel disease. Created with Biorender.com.