Genetic and Functional Profiling of Crohn's Disease: Autophagy Mechanism and Susceptibility to Infectious Diseases

Abstract

Crohn's disease is a complex disease in which genome, microbiome, and environment interact to produce the immunological background of the disease. Disease in childhood is more extensive and characterized by a rapid progression, leading to severe repercussions in the course of the disorder. Several genetic variations have been associated with an increased risk of developing the disease and most of these are also implicated in other autoimmune disorders. The gut has many tiers of defense against incursion by luminal microbes, including the epithelial barrier and the innate and adaptive immune responses. Moreover, recent evidence shows that bacterial and viral infections, as well as inflammasome genes and genes involved in the autophagy process, are implicated in Crohn's disease pathogenesis. The aim of this review is to establish how much the diagnostic system can improve, thus increasing the success of Crohn's disease diagnosis. The major expectation for the near future is to be able to anticipate the possible consequences of the disease already in childhood, thus preventing associated complications, and to choose the best treatment for each patient.

Autoimmunity of Gastrointestinal Tract

“…In mucous membrane function, the disorders of autophagy affect some aspects of innate and acquired inflammatory response, e.g. function of Paneth cells, cytokines production, pathogens clearance and, what was showed in last time, decrease function of goblet cells and absorptive function of microvilli [18,19].…”

“…Like in other chronic inflammatory diseases, the inducing factor is unknown, but it is believed, that interaction between genetic background and environmental factors, mainly intestinal microbiota, leads to the disease. In last 20 years two tendencies are noted: increased number of patients and decrease in age, so children before age of 2 years fulfilling the criteria of CD are observed [19,25,31,53]. The clinical symptoms are very heterogeneous, due to localization of inflammation in any part of gastrointestinal tract from mouth to anus, age of patient, time of process before onset [19].…”

“…In last 20 years two tendencies are noted: increased number of patients and decrease in age, so children before age of 2 years fulfilling the criteria of CD are observed [19,25,31,53]. The clinical symptoms are very heterogeneous, due to localization of inflammation in any part of gastrointestinal tract from mouth to anus, age of patient, time of process before onset [19]. Moreover, in many patients symptoms from gastrointestinal tract are mild or unspecific, but extra-intestinal symptoms signal chronic disease.…”

“…Therapy is adjusted to symptoms and grading of disease at diagnosis. The antibodies to saccharomyces cerevisiae (ASCA) in IgA (and/or IgG class) are detected in high level what suggests increased intestinal barrier permeability and contact of microbiota with immunocompetent cells [19,21,22,53]. Autoantibodies to acinar pancreatic cells are noted in patients with CD localized in proximal jejunum.…”

Docosahexaenoic Acid Attenuated Experimental Chronic Colitis in Interleukin 10–Deficient Mice by Enhancing Autophagy Through Inhibition of the mTOR Pathway

“…Crohn's disease (CD) is a chronic form of inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal tract, ranging from the mouth to the anus 1 . Studies have shown that interleukin 10–deficient (IL‐10 −/− ) mice display similar characteristics to those of human patients with CD 2 .…”