Inflammatory bowel disease with a very early onset

Abstract

Inflammatory bowel disease (Crohn's disease and ulcerative colitis) has a tendency to manifest at earlier age. In childhood (< 6 years of age) it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

Keywords

• inflammatory bowel disease with a very early onset
• immunodeficiency state
• monogenic immune defect