Evaluation and Treatment of Monogenic Forms of Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBDs) are complex disorders that develop in genetically susceptible hosts due to dysregulated immune responses to microbial dysbiosis and environmental changes. Although in the vast majority of cases, the genetic contribution to development of these diseases is small, in rare cases, IBD develops directly as a result of deleterious mutations in the genes involved in immune and epithelial cell function. In these cases, intestinal inflammation is usually severe, which develops in most cases in the first years of life and occasionally is accompanied by recurrent or atypical infections. In this review, the approach to different monogenic disorders that cause IBD is discussed, including mutations in the IL-10 pathway, neutrophil defects, regulatory T-cell disorders, autoinflammatory conditions, epithelial cell diseases, and disorders affecting B- and T-lymphocyte dysfunction. Moreover, a multidisciplinary diagnostic approach is suggested, which highlights in which cases a monogenic disorder should be suspected. This review contains 3 figures, 3 tables, and 42 references. Key Words: inflammatory bowel disease, IL-10, chronic granulomatous disease, common variable immune deficiency, epithelial cells, genetics, immune cells, mucosal homeostasis, pathogenesis, very early–onset disease.