2018/12/18 by Julia Pazmandi, Júlia Pázmándi, Artem Kalinichenko +3 · 2 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #IL-33, ST2, and ILC Pathways #Immunodeficiency and Autoimmune Disorders #Inflammatory Bowel Disease
paper · doi:10.1111/imr.12726
openalex publication_date 2018/12/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Rare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early-onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early-onset IBD (VEO-IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections. As for other human diseases, it is likely that adult-onset diseases may represent complex diseases integrating the effects of host genetic susceptibility and environmental triggers. Comparison of adult-onset IBD and VEO-IBD thus provides beautiful models to investigate the relationship between monogenic and multifactorial/polygenic diseases. This review discusses the present and novel findings regarding monogenic IBD as well as key questions and future directions of IBD research.