Crohn's Disease: When Proctection Against Bacteria is Not Sufficient Due to Lack of Weapons
Crohn's disease is a chronic inflammatory disease, affecting most commonly the mucous membranes of the ower part of the small bowel and the colon. It affects approximately 150,000 people in Germany; five new cases per 100,000 inhabitants are diagnosed each year. The cause of the disease is unknown; genetic and environmental factors have been suggested to play a role.
A camera's view of the intestinal tract:
Colonoscopy reveals any unusual condition of the diseased bowel such as inflammation or ulcer.
NGFN scientists trace the cause of Crohn's disease.
Upper photo courtesy of Dr. Siegfried Heuer
Lower photo: NGFN
Colonoscopy reveals any unusual condition of the diseased bowel such as inflammation or ulcer.
NGFN scientists trace the cause of Crohn's disease.
Upper photo courtesy of Dr. Siegfried Heuer
Lower photo: NGFN
An international research team comprising scientists of the German National Genome Research Network investigated the potential role of the defensins in the development of chronic inflammations. Defensins are defense weapons used by the human immune system. They act like our body's own antibiotics that protect the mucous membranes from bacterial invasion.
There are different Defensins in the arsenal of weapons of the human immune system. The building instructions for the defensins - the defensin genes - are arranged in clusters on chromosom 8. The number of defensin genes varies considerably across the population. Some people carry two, others up to ten copies of a specific defensin gene. , gibt verschiedene Defensine im Waffenarsenal des menschlichen Abwehrsystems. Die Bauanleitungen für die Defensine – die Defensin-Gene - liegen auf dem Chromosom 8. Bei den Defensin-Genen gibt es eine Besonderheit. Sie kommen bei jedem Menschen in unterschiedlicher Anzahl vor. Manche Menschen haben nur zwei, andere bis zu zehn Kopien eines bestimmten Defensin-Gens. Die Anzahl der Defensin-Bauanleitungen, die jeder in seinem Erbgut hat, schwankt also innerhalb der Bevölkerung erheblich.
In 2002 the research team has already shown that patients with Crohn's disease of the colon exhibit a lower level of the so-called beta-defensins in the mucous membranes. The scientists now discovered that the number of defensin genes has a crucial impact on the development of Crohn's disease and that many patients with the colonic form of the disease are lacking one copy of the gene coding for the important defense molecule beta-defensin-2.
Healthy persons have an average of four copies of this gene per cell. The research team has now shown that patients with colonic CD have on average only three copies of the gene encoding beta-defensin 2, whereas The researchers showed that a lower number of gene copies is indeed associated with reduced production of the endogenous antibiotic, which explains the known low defensin level. They presume that this causes the defense of the intestinal mucous membrane to become porous so that bacteria can attach to and invade the mucous membrane, which leads to the typical inflammatory hot spots of Crohn's disease.Gesunde Menschen besitzen im Durchschnitt vier Kopien des beta-Defensin-2 – Bauplans. Bei Patienten mit einem Morbus-Crohn-Befall des Dickdarmes findet man im Schnitt nur drei Kopien dieses Gens. Das Wissenschaftlerteam zeigte, dass die geringere Kopienzahl der Gene tatsächlich mit einer verminderten Produktion des körpereigenen Antibiotikums einhergeht. Das erklärt den niedrigen Defensin Spiegel in Morbus Crohn Patienten. Die Wissenschaftler vermuten, dass die Verteidigung der Darmschleimhaut dadurch durchlässig wird.
Jetzt haben die schädlichen Bakterien leichtes Spiel. Da das Abwehrsystem des Körpers geschwächt ist, können sich die Krankheitserreger an die Schleimhaut anheften und in sie eindringen. Es kommt zu den typischen heftigen Entzündungen, die bei Morbus-Crohn-Patienten starke Schmerzen und Krämpfe verursachen.
Website of of scientists involved in this NGFN: German Cancer Research Center, HeidelbergWebsite of of scientists involved in this NGFN: Robert-Bosch-Krankenhaus, Stuttgart
