title: [Crohn's disease - etiopathogenetic factors].
abstract: Crohn's disease is often purely inflammatory, but most patients develop complicated disease with strictures or fistulae. Specific etiopathogenesis of this severe disease is not definitely clear despite research efforts and learning of many pathogenetic mechanisms. Many studies have suggested that NOD2 mutations are associated with increased risk of complicated disease. Presence of NOD2 mutation itself is just one of factors contributing to development of this disease. Genetically predisposed individuals in combination with influence of environmental factors result in a disturbed innate (i.e., disturbed intestinal barrier, Paneth cell dysfunction) and adaptive (i.e., imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. Data of meta-analysis made so far provide ambiguous evidence to support top-down therapy based solely on single NOD2 mutations, but suggest that targeted early-intensive therapy for high-risk patients with two NOD2 mutations might be beneficial, but more prospective trials could answer these questions.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kupka
authors.forename: Jarmila
authors.initials: J
authors.lastname: Símová
authors.forename: Lubomír
authors.initials: L
authors.lastname: Martínek
authors.forename: Pavel
authors.initials: P
authors.lastname: Svoboda
authors.forename: Pavel
authors.initials: P
authors.lastname: Klvaňa
authors.forename: Martina
authors.initials: M
authors.lastname: Bojková
authors.forename: Magdalena
authors.initials: M
authors.lastname: Uvírová
authors.forename: Lenka
authors.initials: L
authors.lastname: Dovrtělová
authors.forename: Petr
authors.initials: P
authors.lastname: Dítě
mesh_terms: D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics
chemical_list: D053473:Nod2 Signaling Adaptor Protein