Crohn's disease

Crohn’s disease, now more frequently referred to as Crohn disease, is an inflammatory bowel disease that, well, causes inflammation of the bowel.

Unlike its cousin, ulcerative colitis, which only affects the large intestine, Crohn disease causes inflammation and tissue destruction anywhere along the gastrointestinal tract, from the mouth to the anus.

Although ulcerative colitis is classified and treated as an autoimmune disease, Crohn disease isn’t technically classified as an autoimmune disease, but rather an immune-related disorder...what does that mean exactly?

Well, with “auto” immune, we think that your own cells and proteins trigger the immune system to start attacking itself.

In Crohn disease, the immune system is thought to be triggered by some foreign pathogen in the gastrointestinal tract.

Several pathogens have been implicated, like Mycobacterium paratuberculosis as well Pseudomona and Listeria species.

So the immune system’s reacting to foreign pathogens...isn’t that what it’s supposed to be doing? Well, yes and no; yes because it’s targeting a foreign invader, no because the inflammatory response is large and uncontrolled and leads to destruction of the cells in the gastrointestinal tract.

So what’s thought to happen is one of these pathogens activates the immune system by antigen presentation, meaning one of the gastrointestinal cells is like “here, I think this is an infectious molecule”, and that’s fine, because it is.

At that point T helper cells, or Th1 cells swoop in and release cytokines—which are cell signaling molecules—like interferon-gamma, and tumor necrosis factor alpha, which further stimulate the inflammatory response.

The cytokines attract Inflammatory cells like macrophages which start releasing even more inflammatory substances like proteases, platelet activating factor, and free radicals, all which contribute to inflammation.

Although not definitively understood, it’s thought that for patients with Crohn disease, one of the steps in this process is dysfunctional and leads to an unregulated and out-of-control inflammatory response.

Unregulated inflammation means lots of proteases, platelet activating factor, and free radicals floating around the gastrointestinal tissue which ultimately causes destruction of healthy tissue.

This dysfunctional immune response is thought to be a product of genetics, and in fact, patients with family members that have Crohn disease are much more likely to develop it themselves.

A number of genes have been identified and are thought to contribute to developing the disease. One of these is a frameshift mutation in the NOD2 gene, now called CARD15.

Usually, for gene expression, nucleotides are read in groups of three... But when you add or subtract one or two nucleotides, it essentially shifts all the remaining nucleotides, usually ends up in totally different amino acids being coded, and probably a dysfunctional protein.

Okay, so the intestinal wall, like this one, has lots of ridges and grooves, and also can be separated into the mucosal layer, submucosal layer, muscle layer, and serosa.