Vnitr Lek 2014, 60(7-8):635-639

Crohn's disease - etiopathogenetic factors

Tomáš Kupka^1,*, Jarmila Šímová^2,3, Lubomír Martínek^3,4, Pavel Svoboda¹, Pavel Klvaňa¹, Martina Bojková¹, Magdalena Uvírová^2,3, Lenka Dovrtělová⁵, Petr Dítě¹

¹ Akademické centrum gastroenterologie Interní kliniky LF OU a FN Ostrava, přednosta doc. MUDr. Arnošt Martínek, CSc.

² Vzdělávací a výzkumný institut AGEL, o.p.s. - pobočka Ostrava-Vítkovice, CGB laboratoř, a.s., Laboratoř molekulární genetiky a patologie, vedoucí Mgr. Jarmila Šimová

³ LF OU Ostrava, děkan doc. MUDr. Jaroslav Horáček, CSc.

⁴ Chirurgická klinika LF OU a FN Ostrava, přednosta doc. MUDr. Pavel Zonča, Ph.D., FRCS

⁵ Katedra podpory zdraví FSS MU Brno, vedoucí katedry Mgr. Lenka Dovrtělová, Ph.D.

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.

Keywords: biologic treatment; Crohn's disease; fenotypization; genetic; imunobiology

Received: May 9, 2014; Published: July 1, 2014  Show citation