Mögliche Auswirkungen auf die Therapie - Defekte Defensinbarriere bei Morbus Crohn

Der Morbus Crohn gehört zusammen mit der Colitis ulcerosa zur Gruppe der chronisch entzündlichen Darmerkrankungen (CED), deren Ursachen trotz intensiver Forschung noch nicht vollkommen geklärt sind. Während bei der Colitis ulcerosa die Entzündung normalerweise nur im Dickdarm vorkommt, kann der Morbus Crohn vereinfacht in Dünn- und Dickdarm-Crohn unterteilt werden. Beide regionalen Lokalisationen sind durch jeweils spezifische Defekte der Defensinabwehr charakterisiert. Bei Patienten mit Dünndarm-Crohn werden die so genannten a-Defensine in den Panethzellen, die neben antimikrobiellen Peptiden auch das Bakterien-Erkennungsmolekül NOD2 exprimieren, vermindert gebildet. Diese Reduktion wird weiter verstärkt, wenn zusätzlich eine Mutation in NOD2 vorliegt. Im Gegensatz dazu zeigen Patienten mit Kolon-Befall eine abgeschwächte Bildungsfähigkeit von b-Defensinen, die normalerweise von Enterozyten gebildet werden, wenn eine Entzündung besteht. Somit könnte ein Defensinmangel wesentlich an der Pathogenese des Morbus Crohn beteiligt sein.

Both Crohn's disease and ulcerative colitis belong to the group of chronic inflammatory intestinal diseases, the causes of which have not been pinpointed so far despite intensive research. Whereas in ulcerative colitis the inflammation is usually limited to the colon, classification of Crohn's disease may be simplified by subdividing it into two categories: Crohn's disease of the enteron and of the colon. Both of these regional localizations are characterised by specific defects in defensin activity. In patients suffering from Crohn's disease of the enteron there is a reduced production of the so-called alpha defensins in Paneth's cells which besides expressing antimicrobial peptides also express the bacterial antigen recognition molecule NOD2. This reduced production is further reduced if there is also a mutation in NOD2. By way of contrast, patients with Crohn's disease of the colon are characterized by a reduced ability to produce b defensins usually produced by enterocytes, if an inflammation is present. Hence, defensin deficiency may be largely involved in the pathogenesis of Crohn's disease.

Key Words

Crohn's disease - ulcerative colitis - defensins - Paneth's cells - NOD2

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