Celiac disease

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Introduction0:00–1:44

It's becoming more and more common to see things like gluten-free pizza or gluten-free buns and other gluten-free items at restaurants, grocery stores or other food based businesses.
This is partly because there's this increasing recognition, awareness and diagnosis of a disease called celiac disease. In the past called celiac sprue as many as one in 100 people have celiac disease, although many remain undiagnosed.
Now, celiac disease is currently understood as an immune system mediated disorder where the gluten in food triggers the body's immune cells to attack the cells in the small intestine as well as produce auto antibodies against tissue transglutaminase.
Also found in the small intestine as well as other tissues like the heart or the liver glutens found in common wheats and grains including wheat, rye and barley.
If we take a look at wheat, you've got your individual wheat kernels and then inside each kernel, there's the endosperm which has a bunch of nutrients for the seeds, embryo, mostly protein and starch and some vitamins.
The type of protein here is gluten. The main culprit in celiac disease.
Well, really the main culprit behind celiac disease is gliadin an umbrella term given to a group of gluten peptides that share a 33 amino acid sequence which triggers an immune response.
So if somebody with celiac disease eats a wheat based pizza, it's broken down in the stomach into gluten peptides and a whole lot of other stuff that other stuff is no challenge for digestion, gluten peptides like the gliadin in wheat, however, are high in proline and glutamine, two amino acids which make it a tough little bugger to digest.
So when the undigested gluten proteins like gliadin get to the small intestine, they meet the intestinal mucosa which is lined with a layer of intestinal epithelial cells, gluten proteins can then get across the gut epithelial cells, either between them or through the cell from the apical to the basolateral membrane and get to the lamina propria which is a thin layer that lines the gut wall.

Pathology1:44–5:54

Once there, an enzyme called tissue transglutaminase or T TG cuts off an amid group from the protein deaminated gluten proteins are then eaten up by macrophages and served up on its MHC class two molecules.
Remember, macrophages are in the gut and are always doing a bit of gut sampling where they grab proteins which a lot of times are from foods that we've eaten and show them to the immune cells.
M HC stands for major histocompatibility complex. And is that name of the serving platter for the stuff that is served up.
It's a normal way to make sure there are no pathogenic bacteria lurking in the gut. Now, there are a ton of different types of MHC class two serving platters and these serving platters are encoded by genes called human leucocyte antigen genes or HLA A genes.
These genes determine what things the MHC class two molecules serve up. So for example, HLA AD R encodes for an MHC that serves up something different than the one HLA DQ encodes for researchers have noticed that patients with celiac disease typically have specific HLA A genes specifically HLA DQ two and HLA DQ eight, which code for M HC serving platters that allow deaminated gliadin to bind tightly.
And when deaminated gliadin is tightly bound to these specific M HC serving platters, that's when the immune system kicks in the macrophage, throws it up top and is like, hey, uh guys, what do you think about this molecule?
And T helper cells also known as CD four plus T cells from the immune system that recognize the gliadin zoom over and are like, yep, I'll take it from here and they release inflammatory cytokines like interferon gamma and tumor necrosis factor, which are molecules that initiate inflammation, directly damaging and destroying epithelial cells in the vili of the small intestine in the process.
Not only that though the helper T cell stimulates B cells to start pumping out IGA antibodies against gliadin and the tissue transglutaminase enzyme of these anti tissue transglutaminase antibodies play a role in some of the non digestive complications of celiac disease, anti gliadin antibodies.
On the other hand, don't cause any damage. They are however helpful in making a diagnosis.
Finally, the helper T cells also recruit killer CD eight plus T cells, which is when things get nasty, killer T cells are drawn to and destroy cells undergoing inflammation.
So, in short, as patients eat gluten, the immune system is stimulated and epithelial cells are destroyed. It's possible that the destruction of these cells lets more gliadin across the epithelium since they're not bunched together as tightly as they were before.
Now, this whole fiasco mainly happens in the duodenum probably because it's the first part of the small intestine. And so the first to be exposed to gluten, the jejunum and ileum are also involved, but the duodenum is where most of the damage goes down.
So, a biopsy of the duodenum shows pretty clearly the extent of the damage, healthy duodenum should look like this where you have these really tall vili and these crypts that don't go down too far with celiac disease.
These vili can be destroyed and flattened out called villous atrophy and the crypts can get longer. These changes are called crypt hyperplasia, possibly from infiltration of immune cells or from the remodeling process that begins to take place during chronic inflammation.
You'll also be able to see this infiltration of immune cells or lymphocytes in the epithelium. An endoscopic biopsy of this tissue is generally recommended for diagnosis and monitoring of celiac disease.

Symptoms5:54–6:37

Children with celiac disease often present with symptoms like abdominal distension or bloating as well as failure to thrive.
And diarrhea, adults typically have chronic diarrhea and bloating as well, but the symptoms vary wildly. Also, patients can frequently have dermatitis, herpetiformis as a complication which actually has nothing to do with the herpes virus.
It's actually a bumpy skin rash that pops up from circulating IGA antibodies in the blood where they mistakenly bind to the transglutaminase in the dermal papillae of the epidermis.
Once they've bound neutrophils swing by and start up an inflammatory reaction that's noticed on the skin as this rash tests for the antibodies in the blood can be used clinically to help screen for celiac disease.

Diagnosis6:37–7:35

IG A blood tests for anti tissue transglutaminase antibodies can be done. And these bear two names depending on the lab technique used to determine them.
So both T TG and endomet TTG antibodies look for the same thing. They can be effective ways to determine whether someone has celiac disease, especially in more severe cases.
Although for more common, mild forms of celiac, these tests are less effective tests for IGA or even IgG antibodies against de amidated gliadin may also be used.
The older anti gliadin antibodies are not very accurate and in general should not be used for reasons that aren't well understood.
People with celiac disease have a somewhat higher risk of being iga deficient, meaning they aren't able to produce any IGA antibodies in general.
So in this case, they'd need to have an IgG screening test done. Now, the main bad guy in this whole story that provokes the immune system and causes this whole mess is gluten.

Treatment7:35–8:35

So, symptoms and issues typically resolve when patients adopt a gluten free diet. For some patients that start to adhere to a glutenfree diet.
Even for many years, there's still an increased risk of refractory disease like small bowel cancer and T cell lymphoma, presumably due to inflammation and immune system activation over time.
While avoidance of gluten can lead to control of celiac disease. This is a challenging diet and removal of all gluten from the diet is nearly impossible.
It's worth mentioning that there's very little solid scientific evidence to back a removal of gluten from the diet unless you do have celiac disease.
Although some people do seem to have improved gi symptoms on a gluten free diet, whether that's from removing gluten specifically or more broadly, an adherence to a diet that's typically much lower in processed foods and carbohydrates remains to be seen.

Review8:35–9:28

All right. As a quick recap, celiac disease is an immune mediated system disorder where the gluten and food triggers the body's immune cells to attack the cells in the small intestine as well as produce autoantibodies against tissue transglutaminase.
Children with celiac disease often present with symptoms like abdominal distension or bloating as well as failure to thrive and diarrhea.
Adults typically have chronic diarrhea and bloating as well. But the symptoms vary wildly.
Blood tests like anti ttg antibodies and anti deamidate gliadin antibodies can be used in addition to small intestinal biopsy to diagnose the disease.
Symptoms of celiac disease improve on a glutenfree diet. But there is little evidence that removal of gluten from the diet has any benefit for people without celiac disease.